Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Huixing Yi; Zheming Li; Xiaoxi Liu; Shijie Dai; Shouye Li

doi:10.1155/2021/9933274

Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Evid Based Complement Alternat Med. 2021 Sep 18:2021:9933274. doi: 10.1155/2021/9933274. eCollection 2021.

Authors

Huixing Yi¹, Zheming Li², Xiaoxi Liu³, Shijie Dai², Shouye Li²

Affiliations

¹ Department of Emergency, First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China.
² College of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang 310000, China.
³ Medical College, Shaanxi Institute of International Trade and Commerce, Xianyang, Shaanxi 712046, China.

Abstract

Background: Lapatinib is a small-molecule tyrosine kinase inhibitor that plays important roles in cell proliferation and survival. Administration of lapatinib with capecitabine is an effective treatment for HER2-positive metastatic BC. However, the effects of lapatinib on gastric cancer (GC) remain to be clear. In this study, we aimed to investigate the therapeutic effects of lapatinib combined with sulforaphane on GC and its underlying mechanisms.

Methods: SGC-7901 and lapatinib-resistant SGC-7901 cells were treated with lapatinib (0.2 μM), sulforaphane (5 μM), or their combinations. Cell viability, invasion, cycle, and apoptosis of SGC-7901 and lapatinib-resistant SGC-7901 cells were evaluated by thiazolyl blue tetrazolium bromide (MTT), Boyden chamber assay, and flow cytometer. The protein expressions of HER-2, p-HER-2, AKT, p-AKT, ERK, and p-ERK were detected by Western blotting.

Results: We observed that lapatinib combined with sulforaphane significantly decreased cell viability and inhibited cell migration of drug-sensitive and drug-resistant cells. Lapatinib sulforaphane also remarkably induced cell apoptosis with G0/G1 arrest. In addition, Western blotting revealed that the expressions of HER-2, p-HER-2, AKT, p-AKT, ERK, and p-ERK were downregulated by lapatinib-sulforaphane treatment.

Conclusion: Combination of lapatinib and sulforaphane might be a novel and promising therapeutic treatment for lapatinib-sensitive or lapatinib-resistant GC patients.