Chinese Herbal Medicine Wenxia Changfu Formula Reverses Cell Adhesion-Mediated Drug Resistance via the Integrin β1-PI3K-AKT Pathway in Lung Cancer

Abstract

In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin β1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin β1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin β1/PI3K/AKT and apoptosis induction.

Effect of Wenxia Changfu Formula Combined With Cisplatin Reversing Non-Small Cell Lung Cancer Cell Adhesion-Mediated Drug Resistance

“…We have already established A549 cells on 3D cell culture system that were incubated with DDP alone or in combination with WCF medicated serum in vitro. With the extension of culture time, when cells formed multicellular colonies, the tolerance of cells to DDP increased, and the sensitivity of cells to DDP decreased (Zhang et al, 2019). In this study, the WCF combined with DDP not only suppressed cell viability on A549 cells and H1299 cells in time and dose-dependent manners but also significantly inhibited the adhesion and migration abilities of tumor cells.…”

Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cells in vitro and in vivo

“…1,2 One of the most prominent obstacles to universally effective chemotherapy remains tumor multidrug resistance (MDR), which is the intrinsic or acquired resistance of tumor cells to a wide range of drugs with diverse structures and functions. 3,4 Numerous studies have validated ATP-binding cassette (ABC) transporters-such as ABCB1 (also called P-glycoprotein), ABCC1 (also called MRP1), and ABCG2 (also called BCRP)-as the main players for MDR to distinct anti-tumor drugs. [5][6][7][8][9] Chemical MDR reversal agents-such as verapamil, 10 cyclosporin A, 11 and tamoxifen 12 have limited application because of their high toxicities, side effects, and unobvious reversal effect when combined with chemotherapies.…”

Qigesan reduces the motility of esophageal cancer cells via inhibiting Gas6/Axl and NF-κB expression

“…Adjuctive therapy with TCM can significantly improve the clinical symptoms of liver cancer, gastric cancer patients on the basis of conventional treatment, and the proportion of distant metastasis in the TCM use was significantly lower than in non-TCM use [50,51]. TCM formula can reverses cell adhesion-mediated drug resistance in lung cancer cells [52]. Some Chinese herbal compounds have been reported to have potential anticancer effects [53].…”