Page 222 - 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-40

Synergistic reversal of multidrug resistance through concurrent modulation

of P-glycoprotein and STAT3 by a polymethoxyflavone derivative

1
,1,2
1
Jo-Ching Wang, I-Ting Wu, Y u -Hsuan Lan, Chin-Chuan Hung*
1

1 Department of Pharmacy, College of Pharmacy, China Medical University, Taichung
406040, Taiwan
2 Department of Pharmacy, China Medical University Hospital, Taichung 404327, Taiwan
* E-mail: cchung@mail.cmu.edu.tw

Abstract
Chemotherapy remains central in cancer treatment, yet its success is frequently limited by
multidrug resistance (MDR). This study investigated whether 3,5,6,7,8,3'-hexamethoxy-4',5'-
methylenedioxyflavone can overcome MDR by targeting both P-glycoprotein (P-gp) and
STAT3. Drug-sensitive KB and resistant KB/Vin cells were employed to evaluate cytotoxicity,
IC₅₀ shifts, and combinational efficacy with chemotherapeutics. The compound markedly
reduced IC₅₀ values, particularly in KB/Vin cells, and SynergyFinder Plus confirmed the
strongest synergy with docetaxel. Cell proliferation assays revealed significant growth
inhibition, while combination treatments induced sub-G1 accumulation and promoted both
early and late apoptosis. Mechanistic studies demonstrated suppression of P-gp activity, verified
by calcein-AM uptake and ATPase assays, together with STAT3 downregulation assessed by
ELISA. Collectively, these findings indicate that this flavone enhances chemotherapeutic
efficacy through dual modulation of P-gp and STAT3 pathways, offering a promising strategy
for overcoming MDR and improving chemotherapy outcomes in resistant cancers.

Keywords: Polymethoxyflavone; Cancer treatment; Multidrug resistance