A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer.
A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer.
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DOI：
10.3892/ijmm.2012.1022
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发表时间：
2012-09
影响因子：
5.4
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Zhang H;Zhou L;Shi W;Song N;Yu K;Gu Y
乳腺癌是女性最常见的癌症。有证据表明，多不饱和脂肪酸（PUFAs）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）影响乳腺癌的增殖、分化和预后。然而，其机制仍不清楚。在本研究中，瞬时受体电位典型（TRPC）3的表达被检测到整个细胞质和细胞表面的MCF-7细胞。这些细胞中的Ca 2+内流是通过二酰甘油类似物（OAG）或细胞内Ca 2+库耗尽激活TRPC 3来诱导的。TRPC介导的Ca ~（2+）内流被PUFA抑制，PUFA包括花生四烯酸（AA）和亚麻酸（LA），但不饱和脂肪酸。过表达的PUFA降解酶，环氧合酶2（COX 2），增强容量的Ca 2+进入。此外，抑制COX 2可降低[Ca 2 +]i。然而，TRPC的抑制减少了细胞周期S期和细胞迁移，暗示了TRP介导的Ca 2+进入细胞增殖和侵袭的功能作用。外源性PUFA和TRPC 3拮抗剂一致地减弱乳腺癌细胞的增殖和迁移，表明PUFA抑制乳腺癌的机制部分通过其抑制TRPC通道。此外，我们的研究结果还表明，TRPC 3似乎是乳腺癌细胞迁移/侵袭的新介质，并代表了一类新的抗癌药物的潜在靶点。
Breast cancer is the most frequent cancer in women. Evidence suggests that the polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) affect breast cancer proliferation, differentiation and prognosis. However, the mechanism still remains unclear. In this study, the expression of transient receptor potential canonical (TRPC)3 was detected throughout the cell cytoplasm and at the cell surface of MCF-7 cells. Ca2+ entry was induced in these cells via activated TRPC3 by either the diacylglycerol analogue (OAG) or by intracellular Ca2+ store depletion. TRPC-mediated Ca2+ entry was inhibited by PUFAs including arachidonic acid (AA) and linolenic acid (LA) but not saturated fatty acids. Overexpression of the PUFA degradation enzyme, cyclooxygenase 2 (COX2), enhanced capacitative Ca2+ entry. In addition, inhibition of COX2 reduced [Ca2+]i. Nevertheless, inhibition of TRPC reduced the cell cycle S phase and cell migration, implicating a functional role for TRP-mediated Ca2+ entry in cell proliferation and invasion. Exogenous PUFA as well as a TRPC3 antagonist consistently attenuated breast cancer cell proliferation and migration, suggesting a mechanism in which PUFA restrains the breast cancer partly via its inhibition of TRPC channels. Additionally, our results also suggest that TRPC3 appears as a new mediator of breast cancer cell migration/invasion and represents a potential target for a new class of anticancer agent.
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