MULBERROSIDE A EXTRACT ENHANCES THE ANTITUMOR EFFICACY OF PACLITAXEL BY INHIBITING THE HIF-1Α/SHH SIGNALING PATHWAY IN LEWIS LUNG CARCINOMA-BEARING MICE Authors: Aiqin Liu, Bing Yan, Richeng Jiang Journal: Journal of Animal and Plant Sciences (JAPS) ISSN: 1018-7081 (Print), 2309-8694 (Online) Volume: 36 Issue: 6 Year: 2026 DOI: https://doi.org/10.36899/JAPS.2026.6.0149 URL: https://doi.org/https://doi.org/10.36899/JAPS.2026.6.0149 Publisher: Pakistan Agricultural Scientists Forum Abstract:

The present work set out to determine whether Mulberroside A (MA) extract could boost the antitumor efficacy of paclitaxel (PTX) in Lewis lung carcinoma (LLC)-bearing mice through modulation of the HIF-1α/SHH signaling pathway. LLC-bearing C57BL/6 mice were randomized into control, model, PTX, MA, PTX+MA, PTX+MA+HIF-1α inhibitor (YC-1) and PTX+MA+SHH inhibitor (Cyclopamine) groups. Tumor growth, apoptosis (TUNEL), microvascular density (MVD and CD31 staining), and histopathology (H&E) were assessed. Expression of HIF-1α/SHH pathway components and downstream targets (VEGF, Bcl-2 and caspase-3) was measured by qPCR, and Western blot.  PTX+MA synergistically inhibited tumor growth and reduced MVD versus PTX alone (P≤0.05), while a higher level of apoptotic cells was observed (P≤0.05). This was accompanied by downregulation of HIF-1α, SHH, SMO, GLI1, VEGF, and Bcl-2, and upregulation of caspase-3 (P≤0.05). Addition of HIF-1α or SHH inhibitors partially reversed these effects, confirming pathway involvement. MA enhances PTX antitumor efficacy in LLC-bearing mice by suppressing the HIF-1α/SHH axis, thereby inhibiting angiogenesis and promoting apoptosis. This combination may represent a potential strategy to improve chemotherapy efficacy in lung cancer.

Keywords: Mulberroside A extract; HIF-1α/SHH pathway; lung cancer; tumor-bearing mice; paclitaxel