Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.
Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.
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c-Myc-Max 异二聚化抑制剂 100258-F4 在卵巢癌细胞中的抗肿瘤作用评估。
DOI：
10.1186/s12967-014-0226-x
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发表时间：
2014-08-21
影响因子：
7.4
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Wang J;Ma X;Jones HM;Chan LL;Song F;Zhang W;Bae-Jump VL;Zhou C
卵巢上皮性癌是妇科恶性肿瘤中死亡率最高的一种，因其起病隐匿、复发难治且对化疗耐药。癌基因c-Myc的过度表达是卵巢癌中最常见的事件之一。破坏c-Myc及其下游靶基因的功能是一种很有前途的癌症治疗策略。我们的目的是评估小分子c-Myc抑制剂10058-F4对卵巢癌细胞的潜在作用以及10058-F4发挥其作用的潜在机制。通过MTT法、克隆形成法、流式细胞术和Annexin V FITC法检测，我们发现10058-F4通过诱导细胞凋亡和细胞周期G1期阻滞，以剂量依赖的方式显著抑制SKOV 3和Hey卵巢癌细胞的增殖。用10058-F4处理降低了SKOV 3和Hey细胞中的细胞ATP产生和ROS水平。10058-F4处理的卵巢癌原代培养物在18例中的15例中显示出caspase-3活性的诱导和细胞增殖的抑制。对10058-F4的反应与卵巢癌原代培养物中c-Myc蛋白的过表达水平无关。这些新的发现表明，卵巢癌细胞的生长依赖于c-MYC活性，靶向c-Myc-Max异源二聚化可能是卵巢癌的潜在治疗策略。
Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.
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影响因子：
3
作者：
Haglund, Caroline;Aleskog, Anna;Lindhagen, Elin
通讯作者：
Lindhagen, Elin
影响因子：
3.9
作者：
Joo, Won Deok;Lee, Ji Young;Nam, Joo-Hyun
通讯作者：
Nam, Joo-Hyun
影响因子：
4.9
作者：
He C;Rong R;Liu J;Wan J;Zhou K;Kang JX
通讯作者：
Kang JX
影响因子：
8
作者：
Yin, XY;Giap, C;Prochownik, EV
通讯作者：
Prochownik, EV
影响因子：
3.8
作者：
Kim, Jongchan;Roh, Meejeon;Abdulkadir, Sarki A.
通讯作者：
Abdulkadir, Sarki A.