Triptolide enhances anti-cancer activities of irinotecan in human colon cancer HT-29 cells in vitro and HT-29 cell xenograft tumor model in nude mice.

Abstract

Irinotecan (IRI), a clinically used anticancer drug, is effective against various solid tumors, including colorectal cancer, but its use is limited by side effects. Triptolide (TP), an alkaloid from Tripterygium wilfordii, has been used to treat malignancies in China, though its combined effects with IRI on colon cancer cells are not well-documented. In vitro, human colon cancer HT-29 cells were treated with IRI, TP, or both combinations. Results showed that the combination of IRI and TP significantly decreased viable cell numbers more than IRI or TP alone. IRI combined with TP also led to higher Bax and lower Bcl-2 levels, as well as increased cleaved caspase-8, -9, and -3. These findings suggest that TP enhances apoptosis in HT-29 cells and may potentiate the anticancer effects of IRI by disrupting the balance of pro- and anti-apoptotic proteins, which plays a crucial role in controlling tumor cell survival. In vivo, HT-29 cell-xenograft nude mice were treated with IRI, TP, or both combinations for 30 days. Tumor volume and body weight were measured every 2 days, and liver and kidney functions (ALT, AST, CREA, GGT) were assessed. H&E staining of tissues revealed no significant toxicity in the heart, lungs, liver, kidneys, spleen, or small intestine, suggesting that the combination therapy does not induce major organ damage. Immunohistochemical (IHC) analysis showed that IRI combined with TP resulted in higher expression of cleaved-caspase-3, -8, and -9 compared to IRI or TP alone, indicating enhanced tumor cell apoptosis. These results suggest that TP enhances IRI's anti-cancer effects by promoting apoptosis in colon cancer cells. TP may thus serve as a potential enhancer for IRI in future colon cancer treatments, offering a novel strategy to improve therapeutic outcomes, enhance drug efficacy, and minimize side effects.