Triptolide inhibits proliferation and invasion of colorectal cancer cells by blocking Nrf2 expression.

Wang, Hui‐feng; Zhao, Zhi‐long

Triptolide (TPL), the main active ingredient of Tripterygium wilfordii, has anti‐inflammatory, immunomodulatory, and antitumor actions. It can also inhibit cell proliferation and metastasis while promoting apoptosis of several tumors, such as colorectal cancer (CRC). However, the mechanism of TPL against CRC is not clear. This study was designed to investigate the effects and molecular mechanisms of TPL on the proliferation and invasion ability of CRC cells. A human CRC cell line (HT29 cell line) cultured in vitro was treated with different concentrations of TPL (0, 25, 50, and 100 nmol/L). The proliferation of cells was detected by MTT, the invasion ability of cells by Transwell, and the apoptosis level by flow cytometry. The protein expression levels of nuclear factor‐erythroid 2‐related factor 2 (Nrf2), matrix metalloproteinase (MMP)‐2, and MMP‐9 were detected by western blotting. After transfection with sh‐Nrf2, HT29 cells were divided into NC group, NC TPL group and sh‐Nrf2 TPL group, and the above assays were repeated for each group. TPL significantly inhibited the proliferation and invasion ability of HT29 cells and promoted apoptosis (p <.05). Notably, its inhibitory or promotional effects were concentration‐dependent, which were enhanced with increasing drug concentration (p <.05). After silencing Nrf2 expression, the proliferation, and invasion ability of HT29 cells were further significantly inhibited while cells apoptosis was further promoted (p <.05). Besides, the decreased Nrf2 expression reduced the protein expression levels of MMP‐2 and MMP‐9 (p <.05). TPL can effectively inhibit the proliferation and invasion while promoting apoptosis of HT29 cells. And its mechanism of action may be related to the inhibition of Nrf2 signaling expression.

COLORECTAL cancer; CANCER cells; NUCLEAR factor E2 related factor; TRIPTOLIDE; INHIBITION of cellular proliferation

Chemical Biology & Drug Design, 2024, Vol 103, Issue 1, p1

1747-0277

Academic Journal

10.1111/cbdd.14410