Ophiopogonin B inhibits triple-negative breast cancer progression via suppressing PTP1B and regulating the PI3K/Akt...

This study aimed to investigate whether ophiopogonin B (OP-B), suppresses the progression of triple-negative breast cancer (TNBC) by modulating protein tyrosine phosphatase 1B (PTP1B) activity and the downstream PI3K/Akt signaling pathway.

The anti-TNBC effects of OP-B on MDA-MB-231 and BT549 cells were evaluated using CCK-8, colony formation, wound healing, and Transwell assays. Cell apoptosis was assessed by TUNEL staining. PTP1B gain- and loss-of-function models were established via lentiviral transduction. Protein expression of PTP1B, PI3K, p-PI3K, Akt, and p-Akt was examined by Western blot. The in vivo antitumor activity of OP-B was investigated in a TNBC xenograft model, with subsequent IHC, TUNEL, and Western blot analyses of tumor tissues.

OP-B inhibited the proliferation, migration, and invasion of TNBC cells in a concentration-dependent manner and induced apoptosis. Western blot analysis revealed that OP-B treatment down-regulated the expression of PTP1B protein and suppressed the activity of the PI3K/Akt pathway. Genetic rescue experiments confirmed the critical role of PTP1B: knocking down PTP1B both mimicked and potentiated the antitumor effects of OP-B and its inhibition of the PI3K/Akt pathway, whereas overexpressing PTP1B antagonized these effects. In the MDA-MB-231 cell xenograft mouse model, OP-B treatment significantly inhibited tumor growth, reduced the percentage of Ki67-positive cells in tumor tissues, increased apoptosis, and recapitulated the suppression of the PTP1B/PI3K/Akt signaling axis.

Collectively, these findings indicate that ophiopogonin B exerts anti-tumor effects against triple-negative breast cancer both in vitro and in vivo through modulating PTP1B and suppressing the downstream PI3K/Akt signaling pathway.