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. 2021 Sep 18:2021:9933274.
doi: 10.1155/2021/9933274. eCollection 2021.

Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Huixing Yi  1 , Zheming Li  2 , Xiaoxi Liu  3 , Shijie Dai  2 , Shouye Li  2
Affiliations

Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Huixing Yi et al. Evid Based Complement Alternat Med. .

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.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
The effect of lapatinib, sulforaphane, and their combination on cell viability of SGC-7901 and lapatinib-resistant SGC-7901 cells were measured by MTT assay. Each point is mean (±SE) of two experiments done in triplicate.
Figure 2
Figure 2
Combination of lapatinib with sulforaphane inhibits cell migration as compared to activity of each agent alone. Data presented the mean value of three independent experiments, ∗P < 0.05, ∗∗P < 0.01, and #P < 0.001.
Figure 3
Figure 3
Cell cycle was measured by PI staining assay. (a) Cell cycle of SGC-7901. (b) Cell cycle of lapatinib-resistant SGC-7901. Data presented the mean ± standard deviation of three independent experiments, ∗P < 0.05 and ∗∗P < 0.01.
Figure 4
Figure 4
Cell apoptosis was measured by Annexin V-FITC/PI double staining assay. (a) Cell apoptosis of SGC-7901. (b) Cell apoptosis of lapatinib-resistant SGC-7901. Data presented the mean ± standard deviation of three independent experiments, ∗P < 0.05, ∗∗P < 0.01, and #P < 0.001.
Figure 5
Figure 5
The protein expression levels of HER2, p-HER2, AKT, p-AKT, ERK, and p-ERK were measured by Western blotting. (a) The expressions of HER2, p-HER2, AKT, p-AKT, ERK, and p-ERK in SGC-7901. (b) The expressions of HER2, p-HER2, AKT, p-AKT, ERK, and p-ERK in lapatinib-resistant SGC-7901. Data presented the mean ± standard deviation of three independent experiments, ∗P < 0.05 and ∗∗P < 0.01.
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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R. L., Torre L. A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Sitarz R., Skierucha M., Mielko J., Offerhaus J., Maciejewski R., Polkowski W. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Management and Research. 2018;10:239–248. doi: 10.2147/cmar.s149619. - DOI - PMC - PubMed
    1. Guggenheim D. E., Shah M. A. Gastric cancer epidemiology and risk factors. Journal of Surgical Oncology. 2013;107(3):230–236. doi: 10.1002/jso.23262. - DOI - PubMed
    1. Bai M., Song N., Che X., Wang X., Qu X., Liu Y. Chk1 activation attenuates sensitivity of lapatinib in HER2-positive gastric cancer. Cell Biology International. 2018;42(7):781–793. doi: 10.1002/cbin.10922. - DOI - PubMed
    1. Zhao L., Liu Y., Tong D., et al. MeCP2 promotes gastric cancer progression through regulating FOXF1/Wnt5a/β-catenin and MYOD1/caspase-3 signaling pathways. EBioMedicine. 2017;16:87–100. doi: 10.1016/j.ebiom.2017.01.021. - DOI - PMC - PubMed

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