Triptolide inhibits proliferation and invasion of colorectal cancer cells by blocking Nrf2 expression
Hui-Feng Wang1, Zhi-Long Zhao1
1The Second General Surgery Department, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Abstract:
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.
Insights
Triptolide (TPL) effectively inhibits colorectal cancer (CRC) cell proliferation and invasion while promoting apoptosis. Its mechanism involves downregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling, impacting MMP-2 and MMP-9 expression.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triptolide (TPL), derived from Tripterygium wilfordii, exhibits anti-inflammatory, immunomodulatory, and antitumor properties.
- TPL has demonstrated potential in inhibiting cancer cell proliferation, metastasis, and inducing apoptosis in various tumors, including colorectal cancer (CRC).
- The precise molecular mechanisms underlying TPL's anti-CRC effects remain incompletely understood.
Purpose of the Study:
- To investigate the effects of TPL on the proliferation and invasion of human colorectal cancer (HT29) cells in vitro.
- To elucidate the molecular mechanisms by which TPL exerts its anti-cancer effects in CRC.
- To determine the role of nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling in TPL's action against CRC.
Main Methods:
- HT29 cells were treated with varying concentrations of TPL (0-100 nmol/L).
- Cell proliferation, invasion, and apoptosis were assessed using MTT assays, Transwell assays, and flow cytometry, respectively.
- Protein expression of Nrf2, MMP-2, and MMP-9 was analyzed via Western blotting, with Nrf2 further silenced using sh-Nrf2.
Main Results:
- TPL significantly inhibited HT29 cell proliferation and invasion in a dose-dependent manner.
- TPL treatment significantly promoted apoptosis in HT29 cells, with effects intensifying at higher concentrations.
- Silencing Nrf2 expression further enhanced TPL's inhibitory effects on proliferation and invasion, and boosted apoptosis, while reducing MMP-2 and MMP-9 levels.
Conclusions:
- TPL demonstrates significant efficacy in inhibiting colorectal cancer cell proliferation and invasion, while simultaneously promoting apoptosis.
- The anti-cancer mechanism of TPL in CRC appears to be mediated through the inhibition of Nrf2 signaling pathway.
- Targeting the Nrf2 pathway represents a potential therapeutic strategy for enhancing TPL's effectiveness against colorectal cancer.
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