Tanshinone IIA may inhibit the growth of small cell lung cancer H146 cells by up-regulating the Bax/Bcl-2 ratio and decreasing mitochondrial membrane potential
Tanshinone IIA may inhibit the growth of small cell lung cancer H146 cells by up-regulating the Bax/Bcl-2 ratio and decreasing mitochondrial membrane potential
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DOI：
10.3892/mmr_00000310
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发表时间：
2010-07-01
影响因子：
3.4
通讯作者：
Su, Chin-Cheng
中科院分区：
文献类型：
--
作者：
Cheng, Chun-Yuan;Su, Chin-Cheng
丹参酮IIA（Tan-IIA）对人非小细胞肺癌A549细胞的生长有抑制作用。然而，这种恶性肿瘤背后的分子机制尚未建立。在本研究中，我们研究了Tan-IIA在体外对人小细胞肺癌H146细胞的作用。MTT法检测Tan-IIA对H146细胞的细胞毒性。流式细胞仪检测H146细胞线粒体膜电位（MMP）、活性氧（ROS）和Ca 2+的变化; Western blotting检测Bax、Bcl-2、Caspase-3、NF-κ Bp 65、GADD 153和β-actin蛋白的表达。H146细胞呈剂量依赖性抑制。Tan-IIA（5 μ g/ml）作用H146细胞24 h后，GADD 153和Caspase-3蛋白表达增加，而原癌基因bcl-2蛋白表达明显下降。流式细胞仪显示Tan-IIA可增加细胞内ROS和Ca ~（2+）的生成，但降低MMP的生成。结果表明，Tan-IIA能够抑制H146细胞的增殖。这种作用背后的分子机制之一可能是诱导ROS释放和MMP的降低，MMP的降低由Bax/Bcl-2比值的增加引起。另一种可能是内质网应激引起的Ca ~（2+）释放，GADD_（153）表达增加，Bcl-2表达降低，Bax/Bcl-2比值升高，MMP降低，Caspase-3表达增加，从而抑制H146细胞。因此，Tan-IIA可能是一种很有前途的治疗人小细胞肺癌H146细胞的新型化疗药物。
Tanshinone IIA (Tan-IIA) may inhibit the growth of human non-small cell lung cancer A549 cells. However, the molecular mechanisms behind this malignancy have yet to be established. In the present study, we examined the effects of Tan-IIA on human small cell lung cancer H146 cells in vitro. The cytotoxicity of Tan-IIA in H146 cells was measured using the MTT assay. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and Ca2+ in H146 cells were detected by flow cytometry, and the protein expression of Bax, Bcl-2, Caspase-3, NF-kappa Bp65, GADD153 and (beta-actin in H146 cells was measured by Western blotting. H146 cells were inhibited in a dose-dependent manner. The protein expression of GADD153 and Caspase-3 was increased, but the proto-oncogene bcl-2 was notably decreased in H146 cells treated with Tan-IIA (5 mu g/ml) for 24 h. FACS showed that Tan-IIA may increase the production of ROS and Ca2+, but decreases MMP. The results indicate that Tan-IIA is capable of inhibiting the proliferation of H146 cells. One of the molecular mechanisms behind this effect may be the induction of ROS release and the decrease in MMP caused by an increase in the Bax/Bcl-2 ratio. Another may involve endoplasmic reticulum stress caused by the release of Ca2+ and an increase in GADD153 expression followed by a decrease in Bcl-2 expression, which induces a higher ratio of Bax/Bcl-2, in turn causing a decrease in M MP and leading to an increase in Caspase-3 expression and the inhibition of H146 cells. Thus, Tan-IIA may be a promising novel chemotherapeutic agent for the treatment of human small cell lung cancer H146 cells.