Traditional Chinese medicine formula T33 inhibits the proliferation of human colorectal cancer cells by inducing autophagy.

Traditional Chinese medicine formula T33 inhibits the proliferation of human colorectal cancer cells by inducing autophagy.
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DOI:
10.1002/tox.23460
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发表时间:
2022-05
影响因子:
4.5
通讯作者:
Hsu, Tsai-Ching
Hsu, Tsai-Ching
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Yu-Te;Tzang, Bor-Show;Yow, JiaLe;Chiang, Yi-Hsuan;Huang, Chih-Yang;Hsu, Tsai-Ching

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结直肠癌(CRC)是全球癌症相关死亡的主要原因。尽管手术仍然是结直肠癌治疗的主要方法,但越来越多地采用中医等替代疗法来治疗结直肠癌。我们之前的研究表明T33(一种中药方剂)具有抗乳腺癌活性。有趣的是,据报道,T33 的主要成分白芍对结直肠癌细胞具有抗增殖作用。因此,本研究进一步验证了T33在体外和体内对HT-29和Caco2细胞的影响。进行活力和迁移测定来分析 T33 对 HT-29 和 Caco2 细胞增殖和迁移活性的影响。进行免疫荧光 (IF) 染色和免疫印迹以确认 HT-29 和 Caco2 细胞中 T33 诱导的自噬。生成异种移植 HT-29 肿瘤来测试 T33 的体内作用。在用 T33 处理的 HT-29 和 Caco2 细胞中观察到存活率和迁移活性显着降低,并且 LC3-II 蛋白明显增加。在 T33 处理的 HT-29 和 Caco2 细胞中,p62/SQSTM1 蛋白显着降低,LC3-II/LC3-I 比率增加,Atg7、Atg5 和 Beclin-1 蛋白含量升高。此外,接受 200 或 600 mg/kg T33 治疗的小鼠的异种移植 HT-29 肿瘤体积显着低于对照组小鼠。这些发现表明 T33 通过诱导自噬发挥抗 CRC 活性,并表明 T33 在 CRC 治疗中的潜力。
Colorectal cancer (CRC) is a leading cause of cancer‐related death globally. Although surgery is still the major method for CRC therapy, the adoption of alternative treatments, such as traditional Chinese medicine (TCM), for CRC treatment is increasing. Our previous study has indicated the anti‐breast cancer activity of T33 (a TCM formula). Interestingly, a major ingredient in T33, Baishao (Paeoniae Radix Alba), was reported to have antiproliferative effects on CRC cells. Therefore, this study further validated the influences of T33 on HT‐29 and Caco2 cells both in vitro and in vivo. Viability and migration assays were performed to analyze the influences of T33 on proliferation and migratory activity of HT‐29 and Caco2 cells. Immunofluorescence (IF) staining and immunoblotting were performed to confirm T33‐induced autophagy in HT‐29 and Caco2 cells. Xenograft HT‐29 tumors were generated to test the effects of T33 in vivo. Significantly reduced survival and migratory activity were observed in both HT‐29 and Caco2 cells treated with T33 along with apparently increased LC3‐II protein. Significantly decreased p62/SQSTM1 protein, increased LC3‐II/LC3‐I ratio, and elevated amounts of Atg7, Atg5, and Beclin‐1 proteins were detected in both HT‐29 and Caco2 cells treated with T33. Moreover, the volume of xenograft HT‐29 tumors was significantly lower in mice receiving 200 or 600 mg/kg T33 than in control‐treated mice. These findings indicate that T33 exerts anti‐CRC activity by inducing autophagy and suggest the potential of T33 for CRC treatment.
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