Astragaloside IV targets TUBB4B to inhibit proliferation and promote apoptosis of pituitary tumor cells via the STMN1/ERK pathway

Pituitary tumors, as common intracranial neoplasms, present challenges in clinical management because of high postoperative recurrence rate, drug resistance and pronounced side effects. Astragaloside IV (AS‑IV), the primary active component of the traditional Chinese herb Astragalus membranaceus, has antitumor activity in numerous types of Cancer. However, its effects and mechanisms in pituitary tumors remain unclear. The present study aimed to investigate the effects of AS‑IV on proliferation and Apoptosis of pituitary tumor cells and to elucidate its molecular mechanisms. Cell Counting Kit‑8 (CCK‑8), TUNEL, EdU, immunohistochemistry (IHC), and Western blotting, among Others, showed that AS‑IV significantly suppressed the viability of the rat pituitary tumor cell lines GH3 and MMQ in a concentration‑ and time‑dependent manner while inducing Apoptosis. Tubulin β4B Class IVb (TUBB4B) was highly expressed in pituitary tumor tissue and its overexpression promoted cell proliferation while inhibiting Apoptosis. AS‑IV bound TUBB4B with high affinity, forming a stable complex. TUBB4B regulation influenced pituitary tumor cell sensitivity to AS‑IV, with AS‑IV demonstrating enhanced antitumor efficacy in TUBB4B‑overexpressing tumors. TUBB4B activated the ERK/MAPK signaling pathway by upregulating Stathmin 1 (STMN1) expression, which promoted G1/S phase transition. The ERK‑specific inhibitor U0126 reversed this pro-proliferative effect. To the best of our knowledge, the present study is the first to reveal that AS‑IV inhibits pituitary tumor proliferation and promotes Apoptosis by targeting TUBB4B to regulate the STMN1‑ERK signaling axis, providing a novel theoretical basis and potential strategies for traditional Chinese medicine treatment and molecular targeted research on pituitary tumors.