Antitumor activity of antisense oligonucleotide p45Skp2 in soft palate carcinoma cell squamous in vitro

• Główni autorzy: Supriatno Supriatno (Autor), Sartari Entin Yuletnawati (Autor), Iwa Sutardjo Rus Sudarso (Autor)
• Format: Książka
• Wydane: Universitas Airlangga, 2013-03-01T00:00:00Z.
• Hasła przedmiotowe: article
• Dostęp online: Connect to this object online.

Streszczenie

<p><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Background: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Human soft palate cancers are characterized by a high degree of local invasion and metastasis to the regional </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>lymph nodes. Treatment options for this cancer are limited. However, a new strategy for refractory cancer, gene therapy is watched </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>with keen interest. p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>gene as a tumor promoter gene is one of target of the oral cancer therapy. To inhibit the activity of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>gene is carried-out the genetic engineering via antisense technique. </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Purpose: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>To examine the antitumor activity of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>antisense </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>(p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS) gene therapy in human soft palate [Hamakawa-Inoue (HI)] cancer cells. </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Methods: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Pure laboratory experimental study </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>with post test only control group design was conducted as a research design. To investigate the apoptosis induction of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AStransfected cell was evaluated by colorimetric caspase-3 assay and Flow cytometry. Furthermore, to detect the suppression of in </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>vitro HI cell invasion and cell growth of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS-treatment cell was examined by Boyden chamber kit and MTT assay, respectively. </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Results: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>The cell number of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS-treated HI cell was significant decreased when compared with that of p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>sense (p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>S) </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>cells (p<0.05). p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS-treated cell induced apoptosis characterized by an increase in the early and late apoptosis, and activation </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>of caspase-3 (p<0.05). Therefore, suppression of HI cell invasion and cell growth were markedly increased by p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS treatment </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>(p<0.05).
</em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Conclusion: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Antisense oligonucleotide p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>has a high antitumor activity in human soft palate cancer cell, targeting this </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>molecule could represent a promising new therapeutics approach for this type of cancer.</em></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></p><p><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Latar belakang: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Kanker palatum lunak mempunyai karakteristik invasi dan metastasis ke limfonodi regional yang tinggi. Pilihan </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>perawatan kanker tersebut masih sangat terbatas. Walaupun demikian, strategi baru untuk penanganan kanker yaitu terapi gen menjadi </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>pilihan utama. Gen p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>sebagai gen pemacu tumor merupakan salah satu target terapi kanker oral. Untuk menghambat aktivitas </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>gen p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>tersebut dilakukan rekayasa genetik melalui teknik antisense. </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Tujuan: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Menguji aktivitas antitumor gen p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>antisense </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>(p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS) terhadap sel kanker palatum lunak (sel HI). </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Metode: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Jenis penelitian yang digunakan adalah eksperimen laboratorik </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>murni dengan rancangan posttest only control group design.
Induksi apoptosis sel yang ditransfeksi p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS dievaluasi menggunakan </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>uji caspase-3 kolorimetrik dan flow cytometry. Untuk mendeteksi hambatan invasi dan pertumbuhan sel HI yang ditransfeksi p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS dilakukan uji Boyden chamber dan uji MTT. </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Hasil: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Pertumbuhan sel HI yang ditransfeksi p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS menurun secara signifikan </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>dibandingkan dengan p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Sense (S) (p<0,05). Sel HI transfeksi p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS menginduksi apoptosis dengan meningkatkan aktivitas </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>proteolitik caspase-3 dan early and late apoptosis (p<0,05). Hambatan invasi dan pertumbuhan sel HI secara signifikan meningkat </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>pada sel yang diperlakukan dengan p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS (p<0,05). </em><span style="font-family: Tribune-Bold; font-size: 10pt; color: #231f20; font-style: normal; font-variant: normal;"><strong>Kesimpulan: </strong><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>p45</em><span style="font-family: Tribune-Italic; font-size: 7pt; color: #231f20; font-style: normal; font-variant: normal;"><em>Skp2 </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>AS oligonukleotida mempunyai aktivitas antitumor </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>yang kuat pada sel kanker palatum lunak. Target dari molekul tersebut dapat menjanjikan suatu terapeutik baru untuk jenis kanker </em><span style="font-family: Tribune-Italic; font-size: 9pt; color: #231f20; font-style: normal; font-variant: normal;"><em>palatum tersebut.</em></span></span></span></span></span></span></span></span></span></span></span></span><br style="font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px;" /></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span><br style="font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; orphans: 2; text-align: -webkit-auto; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px;" /></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></p>

Deskrypcja

1978-3728
2442-9740
10.20473/j.djmkg.v46.i1.p18-22