Abstrak 
Akt–the Mammalian Target of Rapamycin (mTOR) Pathway Inhibition Increases Cervical Cancer Cell Chemosensitivity to Active Form of Irinotecan (SN-38)
Leri Septiani, Yudi Mulyana Hidayat, Yusuf Sulaeman Effendi, Tono Djuwantono, Dimas Erlangga Luftimas, Ahmad Faried
Universitas Padjadjaran, International Journal of Integrated Health Sciences. 2013;1(1) :13–21, Volume 1, Number 1 July 2013, pISSN 2302-1381, eISSN 2338-4506
Bahasa Inggris
Universitas Padjadjaran, International Journal of Integrated Health Sciences. 2013;1(1) :13–21, Volume 1, Number 1 July 2013, pISSN 2302-1381, eISSN 2338-4506
Akt-mTOR pathways anti-neoplastic drugs, cervix cancer cells, LY294002, rapamycin
Objective: To investigate the molecular pathway of the cytotoxic effect of SN-38 in human cervical cancer cell lines. Methods: Two human cervical cancer cell lines were treated with various concentrations of irinotecan for 24–72 hours and the sensitivity was analysed using the MTT assay. Apoptosis was further observed through microscopic examinations. The protein expression was determined using Western blot analysis. Results: CaSki cells demonstrated the highest sensitivity to SN-38, whereas HeLa cells showed the lowest. In cervical cancer cells, SN-38 induced apoptosis through an intrinsic- and extrinsic-pathways. In addition, we showed that SN-38 downregulated the phosphorylation of Akt-mTOR pathways in CaSki cells, but not in HeLa cells. Interestingly, in HeLa cells, which were more suggestive of a resistant phenotype, pre-treatment with LY294002 and rapamycin inhibited activation of Akt-mTOR signaling and significantly enhanced the sensitivity of HeLa cells to SN38. Conclusions: Irinotecan exerts its anti-neoplastic effects on cervical cancer cells by inducing apoptosis through caspase-cascade. Inhibition of Akt-mTOR, LY294002 and rapamycin, which is targeted to Akt-mTOR pathways, may sensitize irinotecan-resistant cervical cancer cells.