文献类型：期刊文献

英文题名：Pleione bulbocodioides Polysaccharides Reprogram Tumor-Associated Macrophages via JAK2/STAT3 Inhibition to Suppress Hepatocellular Carcinoma

作者：Yang, Yongjia[1,2];Zhang, Yujie[1,2];Feng, Xiaoyan[2];Gao, Fen[3];Ma, Yanhua[1,2];Yang, Shaojun[1,4]

第一作者：Yang, Yongjia

通信作者：Ma, YH[1];Yang, SJ[1];Ma, YH[2];Yang, SJ[3]

机构：[1]Gansu Univ Chinese Med, Minist Educ, Key Lab Dunhuang Med, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[3]Hubei Coll Chinese Med, Clin Med Coll, Jingzhou, Hubei, Peoples R China;[4]Beihai Hosp Tradit Chinese Med, Beihai, Guangxi, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Minist Educ, Key Lab Dunhuang Med, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[3]corresponding author), Beihai Hosp Tradit Chinese Med, Beihai, Guangxi, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：13

外文期刊名：JOURNAL OF HEPATOCELLULAR CARCINOMA

收录：;Scopus(收录号：2-s2.0-105033679770);WOS:【SCI-EXPANDED(收录号:WOS:001728809500001)】；

基金：This work was supported by the General Project of the Gansu Province Joint Scientific Research Fund (grant no.23JRRA1523, to YanhuaMa) and the Open Fund of the Key Laboratory of Dunhuang Medicine and Transformation, Ministry of Education (grant no. DHYX21-04, to ShaojunYang) .

语种：英文

外文关键词：Pleione bulbocodioides polysaccharides; macrophage polarization; JAK2/STAT3 signaling; hepatocellular carcinoma; tumor immune microenvironment

摘要：Background: Tumor-associated macrophages (TAMs) are key regulators of the immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC). Sustained activation of the JAK2/STAT3 signaling pathway is closely associated with the maintenance of the pro-tumorigenic M2 macrophage phenotype. Pleione bulbocodioides polysaccharides (PBPs) have been reported to exhibit immunomodulatory and antitumor activities; however, whether PBPs regulate TAM polarization in HCC and the involvement of JAK2/STAT3 signaling remain unclear. Methods: The monosaccharide composition and molecular-weight distribution of PBPs were first characterized. Their immunomodulatory effects were evaluated in vitro using IL-4/IL-13-induced M2-polarized RAW264.7 macrophages. In vivo, a Hepa1-6 tumorbearing mouse model was established to assess the effects of PBPs on tumor growth, intratumoral macrophage composition, and JAK2/STAT3 signaling. The JAK2/STAT3 inhibitor AG490 was included as a pharmacological reference. Results: PBPs were identified as high-molecular-weight polysaccharides predominantly composed of mannose and glucose and exhibited no cytotoxicity toward macrophages within the tested concentration range. In vitro, PBPs attenuated M2-associated marker expression and reduced the secretion of immunosuppressive cytokines, including interleukin-10 and transforming growth factor-beta. In Hepa1-6 tumor-bearing mice, PBPs dose-dependently suppressed tumor growth and remodeled intratumoral macrophage composition, characterized by a decrease in M2 macrophages and a concomitant increase in M1 macrophages. These effects were accompanied by suppressed JAK2/STAT3 signaling and coordinated regulation of apoptosis- and angiogenesis-related factors. Conclusion: PBPs suppress HCC progression in association with modulation of TAM polarization and inhibition of JAK2/STAT3 signaling. These findings provide mechanistic insight into the immunomodulatory actions of PBPs and support their further investigation as macrophage-targeting agents for HCC.