Synergistic antitumor effect of combined paclitaxel with FEN1 inhibitor in cervical cancer cells

Publication date: Available online 9 January 2018
Source:DNA Repair
Author(s): Lingfeng He, Huan Yang, Shiying Zhou, Hong Zhu, Huiwen Mao, Zhuang Ma, Ting Wu, Alagamuthu Karthick Kumar, Chandrasekhar Kathera, Avilala Janardhan, Feiyan Pan, Zhigang Hu, Yanhua Yang, Libo Luo, Zhigang Guo
Studies on cervical cancer are urgently required to improve clinical outcomes. As a major anticancer drug for cervical cancer, paclitaxel has been used for many years in clinical therapy but its therapeutic efficacy is limited by common obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of specific DNA repair pathway can sensitize cancer cells to the treatment of chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can be significantly improved when used in combination with FEN1 inhibitor SC13, suggesting a synergistic mechanism between the two compounds. Our studies suggest that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for cervical cancer. Our work also revealed that paclitaxel demonstrates stronger synergistic effect with SC13 than other common used chemical drugs such as doxorubicin, carboplatin or camptothecin on cervical cancer cells.



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