Selective p300 inhibitor C646 inhibited HPV E6-E7 genes, altered glucose metabolism and induced apoptosis in cervical cancer cells

选择性 p300 抑制剂 C646 抑制 HPV E6-E7 基因、改变葡萄糖代谢并诱导宫颈癌细胞凋亡

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作者:Hongpeng He, Yongwei Lai, Yunpeng Hao, Yupeng Liu, Zijiang Zhang, Xiang Liu, Chenhong Guo, Mengmeng Zhang, Hao Zhou, Nan Wang, Xue-Gang Luo, Lihong Huo, Wenjian Ma, Tong-Cun Zhang

Abstract

High risk HPV infection is a causative factor of cervical cancer. The constitutive expression of HPV E6-E7 genes is important for the maintenance of cancer phenotypes. The cellular transcription co-activator p300 plays a crucial role in the regulation of HPV genes thus it was targeted for the inhibition of HPV-associated cervical cancer. In the present study, HPV positive cervical cells were treated with C646, a selective inhibitor of p300, to investigate its influence on HPV E6-E7 expression and cancer cell growth. Results of RT-qPCR, Western-blot and promoter activity assays showed that C646 inhibited the transcription of HPV E6-E7, which was accompanied with the accumulation of p53 protein. Meanwhile, cell proliferation was suppressed, glucose metabolism was disrupted and apoptosis was induced via the intrinsic pathway. Generally, the anti-cervical cancer potential of C646 was demonstrated and a novel mechanism was proposed in this study.

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