Ge Yuqing, Yang Bo, Chen Zhe, Cheng Rubin
National Clinical Research Base of Traditional Chinese Medicine, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7782-8. doi: 10.3892/mmr.2015.4379. Epub 2015 Sep 28.
Pancreatic cancer remains a challenging disease worldwide. Cryptotanshinone (CPT) is one of the active constituents of Salvia miltiorrhiza Bunge and exhibits significant antitumor activities in several human cancer cells. However, the efficacy and molecular mechanism of CPT in pancreatic cancer remains to be elucidated. In the present study, the effect of CPT on the proliferation, apoptosis and cell cycle of human pancreatic cancer cell BxPC‑3 cells was evaluated. The results demonstrated that CPT inhibited proliferation of the BxPC‑3 cells in a concentration‑dependent manner, and significantly induced cell apoptosis and cell cycle arrest. The protein levels of cleaved caspase‑3, caspase‑9 and poly ADP ribose polymerase were upregulated, while the levels of c‑myc, survivin and cyclin D1 were downregulated following treatment with CPT. In addition, CPT decreased the activities of signal transducer and activator of transcription 3 (STAT3) and several upstream regulatory signaling pathways after 24 h. However, CPT only inhibited the phosphorylation of STAT3 Tyr705 within 30 min, without marked effects on the phosphorylation of the other proteins. These results suggested that the inhibition of STAT3 activity by CPT was directly and independent of the upstream regulators in human pancreatic cancer. The present study demonstrated that CPT exerts anticancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human BxPC-3 cells.
胰腺癌在全球范围内仍然是一种具有挑战性的疾病。隐丹参酮（CPT）是丹参的活性成分之一，在多种人类癌细胞中表现出显著的抗肿瘤活性。然而，CPT在胰腺癌中的疗效和分子机制仍有待阐明。在本研究中，评估了CPT对人胰腺癌细胞BxPC-3细胞增殖、凋亡和细胞周期的影响。结果表明，CPT以浓度依赖性方式抑制BxPC-3细胞的增殖，并显著诱导细胞凋亡和细胞周期停滞。用CPT处理后，裂解的半胱天冬酶-3、半胱天冬酶-9和聚ADP核糖聚合酶的蛋白水平上调，而c-myc、生存素和细胞周期蛋白D1的水平下调。此外，CPT在24小时后降低了信号转导和转录激活因子3（STAT3）的活性以及几个上游调节信号通路的活性。然而，CPT仅在30分钟内抑制STAT3 Tyr705的磷酸化，对其他蛋白的磷酸化没有明显影响。这些结果表明，CPT对STAT3活性的抑制在人胰腺癌中是直接的且独立于上游调节因子。本研究表明，CPT通过抑制人BxPC-3细胞中的STAT3信号通路诱导细胞凋亡和细胞周期停滞，从而发挥抗癌作用。
