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TMC120 displayed potent cytotoxic effect on human cervical carcinoma through enhancing the polymerization of microtubules
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Shi, Lilia; Yu, Lea; Zhong, Deshenga; Gu, Chunpinga; Lv, Longyuna; Zeng, Xiaoyuna; Yao, Xinganga; Li, Lina; Liu, Shuwena,b AIDS March 28 2018
Objective: In the post-HAART era, the incidence of some AIDS-defining cancers declined markedly likely reflecting HAART-related improvements in immunity, whereas incidence of some cancers such as cervical cancer has not been affected. Therefore, it is valuable to find whether antiretroviral drugs or prophylactic microbicides could treat or prevent these cancers, especially the cervical cancer.
Design: We screened the anti-HIV drugs, approved or in phase III clinical trials, to identify a potential anticancer drug candidate.
Methods: We chose cervical HeLa and SiHa cancer cells and focused on studying the antitumor effects in vitro and in vivo. Cell proliferation was measured by MTT assay, the cytotoxic effect was obtained through apoptosis as evidenced by Annexin V flow cytometry assay because of the arresting of cancer cells in G2/M phase of cell cycle. Nude mice xenograft model was performed to detect the antitumor effect in vivo.
Results: TMC120 was identified as a potential anticancer drug candidate. TMC120 displayed potent cytotoxic effect on various human cancer cells, including cervical carcinoma cell line HeLa and SiHa. Further mechanism study showed that TMC120 enhanced the polymerization of microtubules, which was followed by mitotic arrest, as well as abnormal mitotic spindles. TMC120 also substantially retarded the growth rate of the tumor in vivo.
Conclusion: TMC120 is a potential chemoprophylactic and therapeutic agent for cervical cancers in a manner similar to paclitaxel, and could be suitable for helping healthy women to prevent HIV infection and cervical cancer.

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