Department of Hepatobiliary and Pancreatic Surgery, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of General Surgery, Sixth People's Hospital Affiliated Shanghai Jiao Tong University, 600 Yi-Shan Road, Shanghai 200233, China.
J Ethnopharmacol. 2019 May 10;235:133-140. doi: 10.1016/j.jep.2019.02.005. Epub 2019 Feb 6.
Radix Scutellariae (RS), the dried root of Scutellariae baicalensis Georgi, known as a herbal medicine in several Asian countries including China, has been widely used to treat inflammation, hypertension, cardiovascular disease as well as cancer. The total flavonoid aglycone extracted (TFAE) was extracted by ethyl acetate and this extraction methodology was optimized and obtained the protection of Chinese patents.
To investigate the underlying mechanism of the chemotherapeutic effects of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo.
We performed CCK8 assays, AnnexinV-FITC/PI staining, flow cytometry assays, transmission electron microscopy, immunofluorescence analysis and Western blot to study the molecular mechanism of TFAE in inducing autophagy and apoptosis in pancreatic cancer cells in vitro and in vivo.
In vitro, TFAE exhibits significant anti-tumor activity against pancreatic cancer cell lines, especially for BxPC3 (IC = 6.5 μg mL). Moreover, TFAE induces apoptosis and autophagy as evidenced by the increased apoptosis or autophagy-related protein level, the increased the fraction of apoptotic cells and the punctuate patterns of LC3 II. Furthermore, TFAE induce autophagy through PI3K/Akt/mTOR inhibition. Interestingly, pharmacological block autophagy by 3-MA enhanced TFAE-induced apoptosis, indicating that TFAE induced autophagy functions as a cytoprotective process against apoptosis. In vivo, 150 mg/kg TFAE inhibited the BxPC3 tumor growth in immune deficient mice with the inhibitory rate of 66.87% and induced both apoptosis and autophagy.
TFAE have anti-tumor activity against pancreatic cancer and can induce apoptosis and autophagy through PI3K/Akt/mTOR signal pathway. TFAE might be a potential anticancer drug to be further developed for human pancreatic cancer therapy.
黄芩（RS）是黄芩的干燥根，在中国和其他几个亚洲国家被用作草药，已被广泛用于治疗炎症、高血压、心血管疾病和癌症。总黄酮苷元提取物（TFAE）是用乙酸乙酯提取的，这种提取方法已经过优化，并获得了中国专利的保护。
研究 TFAE 在体外和体内诱导胰腺癌细胞自噬和凋亡的化疗作用的潜在机制。
我们进行了 CCK8 测定、AnnexinV-FITC/PI 染色、流式细胞术、透射电子显微镜、免疫荧光分析和 Western blot，以研究 TFAE 在体外和体内诱导胰腺癌细胞自噬和凋亡的分子机制。
体外，TFAE 对胰腺癌细胞系具有显著的抗肿瘤活性，尤其是对 BxPC3（IC = 6.5 μg/mL）。此外，TFAE 通过增加凋亡或自噬相关蛋白水平、增加凋亡细胞的比例和 LC3 II 的点状模式来诱导凋亡和自噬。此外，TFAE 通过抑制 PI3K/Akt/mTOR 诱导自噬。有趣的是，用 3-MA 药理学阻断自噬增强了 TFAE 诱导的凋亡，表明 TFAE 诱导的自噬作为一种对抗凋亡的细胞保护过程。在体内，150mg/kg TFAE 抑制免疫缺陷小鼠的 BxPC3 肿瘤生长，抑制率为 66.87%，并诱导凋亡和自噬。
TFAE 对胰腺癌具有抗肿瘤活性，可通过 PI3K/Akt/mTOR 信号通路诱导凋亡和自噬。TFAE 可能是一种有潜力的抗癌药物，可进一步开发用于人类胰腺癌治疗。
