Leri Septiani
Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin General Hospital

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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
International Journal of Integrated Health Sciences Vol 1, No 1 (2013)
Publisher : International Journal of Integrated Health Sciences

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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
Correlation between Protein-with-Molecular-Weight-53 (p53), Burkit Cell Lymphoma 2 (Bcl2), and Fas Ligand (FasL) and Vascular-Cell-Adhesion-Molecule-1 (VCAM-1) mRNA Expression Levels in a Pathogenesis Study of Preeclampsia Teguh, Mintareja; Karkata, Made Kornia; Wirakusumah, Firman Fuad; Mose, Johanes Cornelius; Satari, Mieke Hemiawati; Septiani, Leri
International Journal of Integrated Health Sciences Vol 2, No 1 (2014)
Publisher : International Journal of Integrated Health Sciences

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Objective: To determine the role of protein-with-molecular-weight-53 (p53), burkit cell lymphoma 2 (Bcl2),  Fas ligand (FasL) mRNA, and vascular cell adhesion molecule 1 (VCAM-1), known as the apoptosis-related molecular pathway, in preeclamptic patients.     Methods: Observation on the correlation between the mRNA levels of p53, Bcl2 and FasL and VCAM-1 in 31 subjects at 28-42 weeks gestational age was performed in this study using the real time reverse transcriptase-polymerase chain reaction (RT-PCR).    Results: The results showed that p53 mRNA increased (>1.2350 ng/μL) in the preeclampsia group compared to the normal pregnancy group (p=0.010), Bcl2 mRNA was lower (≤0.9271 ng/μL) in the preeclampsia group than the control group (p=0.041). There was also a tendency of increased FasL mRNA expression (>0.5509 ng/μL) in the preeclampsia group compared to the normal pregnancy group (p=0.300). The level of VCAM-1 elevated (>890.08 ng/mL) in the preeclampsia group compared to the normal pregnancy group (p=0.001). In preeclampsia, the correlation between the Bcl2/p53 ratio and VCAM-1 was r=0.541 (p=0.002), whereas the correlation in normal pregnancy was r=0.099 (p=0.595).     Conclusions: There are correlations between the mRNA expression levels of p53 and Bcl2 as an intrinsic pathway of apoptosis along with the VCAM-1 levels in the incidence of preeclampsia. However, no correlation is found between FasL mRNA expression and the incidence of preeclampsia.Keywords: Bcl2, FasL, p53, Preeclampsia, VCAM-1DOI: 10.15850/ijihs.v2n1.273