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VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway.
Cancer Letters ( IF 9.1 ) Pub Date : 2019-12-03 , DOI: 10.1016/j.canlet.2019.11.035
Vivek K Kashyap 1 , Nirnoy Dan 2 , Neeraj Chauhan 1 , Qinghui Wang 2 , Saini Setua 2 , Prashanth K B Nagesh 1 , Shabnam Malik 1 , Vivek Batra 2 , Murali M Yallapu 1 , Duane D Miller 2 , Wei Li 2 , Bilal B Hafeez 1 , Meena Jaggi 1 , Subhash C Chauhan 1
Affiliation  

In this study, we investigated the therapeutic efficacy of VERU-111 in vitro and in vivo model systems of cervical cancer. VERU-111 treatment inhibited cell proliferation and, clonogenic potential, induce accumulation of p53 and down regulated the expression of HPV E6/E7 expression in cervical cancer cells. In addition, VERU-111 treatment also decreased the phosphorylation of Jak2(Tyr1007/1008) and STAT3 at Tyr705 and Ser727. VERU-111 treatment arrested cell cycle in the G2/M phase and modulated cell cycle regulatory proteins (cyclin B1, p21, p34cdc2 and pcdk1). Moreover, VERU-111 treatment induced apoptosis and modulated the expression of Bid, Bcl-xl, Survivin, Bax, Bcl2 and cleavage in PARP. In functional assays, VERU-111 markedly reduced the migratory and invasive potential of cervical cancer cells via modulations of MMPs. VERU-111 treatment also showed significant (P < 0.05) inhibition of orthotopic xenograft tumor growth in athymic nude mice. Taken together, our results demonstrate the potent anti-cancer efficacy of VERU-111 in experimental cervical cancer models.Thus, VERU-111 can be explored as a promising therapeutic agent for the treatment of cervical cancer.

中文翻译:

VERU-111 通过激活 p53 信号通路抑制宫颈癌细胞的肿瘤生长和转移表型。

在这项研究中,我们研究了 VERU-111 在体外和体内宫颈癌模型系统中的治疗效果。VERU-111 治疗抑制细胞增殖和克隆形成潜力,诱导 p53 的积累并下调宫颈癌细胞中 HPV E6/E7 的表达。此外,VERU-111 处理还降低了 Jak2(Tyr1007/1008) 和 STAT3 在 Tyr705 和 Ser727 处的磷酸化。VERU-111 治疗使细胞周期停滞在 G2/M 期并调节细胞周期调节蛋白(细胞周期蛋白 B1、p21、p34cdc2 和 pcdk1)。此外,VERU-111 处理诱导细胞凋亡并调节 Bid、Bcl-xl、Survivin、Bax、Bcl2 的表达和 PARP 中的切割。在功能测定中,VERU-111 通过调节 MMP 显着降低宫颈癌细胞的迁移和侵袭潜力。VERU-111 治疗还显示出对无胸腺裸鼠原位异种移植肿瘤生长的显着抑制(P < 0.05)。总之,我们的结果证明了 VERU-111 在实验性宫颈癌模型中的有效抗癌功效。因此,可以探索 VERU-111 作为治疗宫颈癌的有前途的治疗剂。
更新日期:2019-12-03
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