Page 219 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-37

WGCNA-guided identification of apoptotic and drug efflux pathways

targeted by tanshinone IIA in multidrug-resistant cancer cells

1,2
,3
1
Lin Erh Cheng, Chin-Chuan Hung, Ching-I Hsu*

1 Department of Pharmacy, China Medical University, No. 100, Section 1, Jingmao Rd.,
Beitun Dist., Taichung 406040, Taiwan
2 Department of Pharmacy, China Medical University Hospital, No. 2, Yude Rd., North Dist.,
Taichung 404332, Taiwan
3 Department of Pharmacy, China Medical University Beigang Hospital, Yunlin, Taiwan
* E-mail: 062897@tool.caaumed.org.tw

Abstract
Tanshinone IIA (TanIIA), an active diterpene quinone, was investigated for its
therapeutic potential in multidrug-resistant (MDR) cancer using KB and vincristine-resistant
KBvin cells. Weighted Gene Co-expression Network Analysis (WGCNA) identified TanIIA-
associated modules significantly enriched in apoptotic regulation, cell cycle control, and ATP-
binding cassette (ABC) transporter activity. Functional enrichment indicated strong
associations with MDR1/P-glycoprotein (P-gp) expression and caspase-mediated apoptosis.
Experimental validation showed that TanIIA increased the sub-G1 cell population in a dose-
dependent manner, with KBvin cells displaying enhanced apoptosis. Calcein-AM uptake assays
confirmed inhibition of P-gp activity, while Western blot and RT-qPCR analyses revealed
significant downregulation of both P-gp gene and protein expression, consistent with WGCNA
predictions. Cell cycle analysis demonstrated S-phase accumulation in resistant cells, aligning
with modules enriched for DNA replication stress and checkpoint regulation. Co-treatment with
paclitaxel significantly enhanced apoptosis in KBvin cells, supporting TanIIA’s
chemosensitizing effect. These findings establish that TanIIA exerts dual effects, promotion of
apoptosis and suppression of P-gp–mediated drug efflux, through molecular pathways
identified by WGCNA. This integrative transcriptomic and functional validation approach
highlights TanIIA as a promising adjuvant candidate for MDR cancer therapy, with pathway-
level insights providing a foundation for further preclinical and translational studies.

Keywords: Tanshinone IIA; Multidrug resistance; P-glycoprotein