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Abstract

Alteration of the apoptosis pathway, as well as the presence of human papilloma virus (HPV), has been linked to the proliferative capacity and drug resistant phenotype of SiHa cervical cancer. We investigated the roles of E6 and E7 HPV oncoproteins in the expression of apoptosis regulating genes in cervical cancer cells that contain the characteristics of apoptosis resistance, and also their correlation with resistance to various apoptosis inducing agents. The expression of the sets of apoptosis regulating genes in both extrinsic (receptor) and intrinsic (non-receptor) pathways were monitored in parental SiHa and multi-drug resistant SiHa (SiHaR) cell lines by RNase protection assay and RT-PCR. An increase in gene expression of intrinsic pathway anti-apoptotic protein Bcl-X L was seen, both at the mRNA and protein levels, in SiHaR compared with SiHa cells, whereas the expression of the genes involved in the extrinsic pathway remained unchanged. SiHaR cells also expressed higher levels of E6 and E7 than did SiHa. Caspase 3 activity was lower in SiHaR compared with that in SiHa cells. A colony formation assay demonstrated enhanced resistance of SiHaR cells to several types of apoptosis inducing agents, including etoposide, doxorubicin, cisplatin, and γ-radiation. Transfection of HPV-negative C33a cells with HPV oncogenes, E7 in particular, induced transcription of Bcl-X L , supporting the role of HPV oncoproteins in affording chemo-radio resistance in cervical cancer.

Photodynamic therapy of cervical cancer by eradication of cervical cancer cells and cervical cancer stem cells

“…The ABCG2 protein has also been found in other cervical cancer cell lines and its presence in side population cells was associated with colony forming efficiency and the capacity to proliferate producing more side population cells and differentiation to more mature cancer cells [38]. Another protein, Bcl-X found in cervical side population confers resistance of cervical cancer to common chemotherapeutic drugs including cisplatin and doxorubicin, and also radiotherapy using γ-radiation [39]. Other numerous markers including high aldehyde dehydrogenase (ALDH) activity and the molecule called Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 have been associated with cervical CSCs to confer resistance of cervical cancer [40, 41].…”