Worldwide, cervical cancer is the second most common cancer in women; approximately 400,000 new cases of this disease are diagnosed each year, of which approximately half will lead to death. Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents. In particular, CaSki cells are much more sensitive than are SiHa cells to cell death induced by doxorubicin and cisplatin. In this study, we compared the proteomic profiles of SiHa and CaSki cells, and identified pathways with the potential to contribute to the differential response. Based on the results from this proteomic analysis, we hypothesized that pathways involved in the regulation of reactive oxygen species (ROS) levels might contribute in to the observed difference in how these two cell lines respondse to chemotherapy. We then extended these findings by analyzing and comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of an RT PCR array, and. We found outdiscovered that cells resistant and sensitive cells to drug treatment had displayed different expression levels of expression of pro- and anti-oxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, to drug-induced cell death, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, the two agents tested, doxorubicin and cisplatin, induced different profiles of ROS, and these differences appear to contribute to the differential sensitivity displayed by cervical cancer cells to treatment. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their differential responses to treatments with chemotherapeutic agents.

Citation Format: Maria Filippova. The response of cervical cancer cells to chemotherapeutic agents depends on endogenous ROS levels as well as the drug-induced ROS profile. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3766. doi:10.1158/1538-7445.AM2014-3766