Affiliation:
1. Department of the 6th of Cancer, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200030,China
2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200030,China
Abstract
Background:
Gefitinib is an important drug used to treat Non-Small Cell Lung Cancer
(NSCLC) with EGFR activating mutations, but drug resistance restricts its clinical application. In this
present study, combined Jin Fu Kang Decoction (JFKD) and gefitinib showed specific cytotoxicity to
gefitinib-resistant cancer cells (PC-9/gef).
Objective:
This study aimed to decipher the molecular mechanism of the JFKD on drug resistance
when used together with Gefitinib and to find the contributing bio-active substance(s) in JFKD based
on the putative mechanism.
Methods:
To investigate the combined effect of gefitinib and JFKD, in vitro experiments were conducted
on the established gefitinib-resistant PC-9 subclone, while in vivo experiments were conducted
on the BALB/c nude mice with PC-9/gef xenografts. Western blot was used to evaluate the protein expression,
and Ultra-Performance Liquid Chromatography (UPLC) coupled with quadrupole time-offlight
Mass Spectrometry (MS) was used to detect the bio-active compounds of JFKD.
Results:
The expression of the PTEN-relevant protein p-EGFR, p-Akt in vitro was inhibited more
when combined JKFD and gefitinib were used, whereas the activities of PDCD4 and PTEN were increased;
remarkably, in vivo experiments showed enhanced tumor growth inhibition when treated with
this combination. Due to this combination, the effect on the gefitinib-resistant cell line, one of the
JFKD-induced anti-cancer mechanisms, was found. To link the putative mechanism and the anticancer
compounds in JFKD, 14 saponins and flavonoids were detected.
Conclusion:
Funder
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Biotechnology
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