International Journal of Integrated Health Sciences
VOL 1, NO 1, July (2013)

Akt–the Mammalian Target of Rapamycin (mTOR) Pathway Inhibition Increases Cervical Cancer Cell Chemosensitivity to Active Form of Irinotecan (SN-38)


Septiani, Leri, Hidayat, Yudi Mulyana, Effendi, Yusuf Sulaeman, Djuwantono, Tono, Luftimas, Dimas Erlangga, Faried, Ahmad



Article Info

Publish Date
17 Sep 2013

Abstract

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 SN-38. 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.Keywords: Akt-mTOR pathways anti-neoplastic drugs, cervix cancer cells, LY294002, rapamycin DOI: 10.15850/ijihs.v1n1.103


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Original Source : http://journal.fk.unpad.ac.id/index.php/ijihs/article/view/103
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Journal Info

Abbrev

ijihs

Publisher

Subject

Health Professions

Description

International Journal of Integrated Health Sciences (IJIHS) is a peer-review journal which publishes original articles, medical research, clinical research and case report. This journal is supported by Faculty of Medicine Universitas Padjadjaran and was launched on September 22nd 2012 and firstly ...