BMC Med：二吲哚甲烷对顺铂减毒增效 联用抗卵巢癌效果更佳

卵巢癌是女性生殖器官常见的肿瘤之一，发病率仅次于子宫颈癌和子宫体癌而列居第三位。2011年，仅在美国一国就有25,000名妇女被确诊患有卵巢癌，并且因罹患卵巢癌而死亡的人数就有15,000多。

近日，来自美国癌症研究人员发现：抗癌新药二吲哚甲烷（DIM）（下边有产品链接）能抑制卵巢癌细胞（我之前记得 貌似DIM 对乳腺癌也有作用）的生长，诱导卵巢癌细胞凋亡，抑制卵巢癌组织的增长。

研究证明二吲哚甲烷能抑制转录因子STAT3的活性，加强化疗药物--顺铂的抗癌活性。

肿瘤细胞的生长过程中伴随着血管生成，二吲哚甲烷不仅能杀死癌细胞，并且能抑制肿瘤的血管生成。肿瘤微环境中的炎症因子IL-6激活STAT转录因子后，促进了肿瘤细胞的生长。90%的卵巢癌患者体内STAT3被激活，二吲哚甲烷通过抑制IL-6的磷酸化降低STAT3的转录活性。

运用顺铂进行化疗治疗的肿瘤病人，病情往往得不到有效控制，即癌症患者出现耐药性。而顺铂的耐药性与STAT3活性的增加有着密切联系。研究者发现：相比较于单独使用顺铂组，顺铂与二吲哚甲烷联合对老鼠体内肿瘤生长的抑制率要高出50%左右。

化疗药物本身毒性很大，并且有严重的不良副作用。靶向作用于STAT3的二吲哚甲烷通过诱导癌细胞凋亡，增强顺铂的化疗效果。同时二吲哚甲烷对正常的卵巢细胞并没有毒性。二吲哚甲烷联与顺铂联用起到了减毒增效的作用。




doi:10.1186/1741-7015-10-9
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Diindolylmethane suppresses ovarian cancer growth and potentiates the effect of cisplatin in tumor mouse model by targeting signal transducer and activator of transcription 3 (STAT3)

Prabodh K Kandala and Sanjay K Srivastava

Background
STAT-3 is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported previously that Diindolylmethane (DIM) inhibits the growth of ovarian cancer cells. However, the exact mechanism by which DIM induces growth suppressive effects was not yet understood and hence evaluated in this report.
Methods
Six human ovarian cancer cells and ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination of cisplatin.
Results
Diindolylmethane treatment induced apoptosis in all the six ovarian cancer cells. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. IL-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, diindolylmethane treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. Diindolylmethane treatment also inhibited cell invasion and angiogenesis by suppressing HIF-1alpha and VEGF. Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation.
Conclusion
These findings provide a rationale for further clinical investigation of diindolylmethane alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.

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