The Effect Of The Small Molecular Drugs Targeting EGFR/PIK3CA On Esophageal Squamous Cell Carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world and especially in China. The five-year survival rate is less than 20%. Multiple molecular alterations exist in the progression of ESCC, including TP53、PIK3CA、CDKN2A、RB1、NOTCH1 and so on. Our lab has found that the EGFR and PIK3CA expressed highly in ESCC. What’s more, they were essential targets for cell growth, proliferation, migariton and metast-asis.MethodThis research based on dysregulated expression of molecular on EGFR and PI3K pathway in ESCC, aiming to screen effective targeting small molecular inhibitors to particular ESCC. Firstly, EGFR was detected in ESCC tissue by means of IHC. Secondly, we detected EGFR in ESCC cell lines by Western Blot. Thirdly, we detected the effect of Erlotinib and Afatinib by means of MTT. Then, CCK-8 was used to estimate the IC50 of Erlotinib, Afatinib and Alpelisib. What’s more, we evaluated the effect of Erlotinib on KYSE450 in mice. The last step, westen blot was conducted to estimate the change of EGFR signal pathway.ResultThe IHC showed overpression of EGFR in ESCC tissue, along with the research published of our lab. The Western Blot showed EGFR were significantly overpressed in KYSE150, KYSE180 and KYSE 450.According to the IC50, We distinguished the ESCC cell line KYSE450 was sensitive to Erlotinib and Afatinib, but not Alpelisib; On contrast, KYSE 150, KYSE 180, KYSE510 were sensitive to Alpelisib, but not Erlotinib or Afatinib. In the in-vivo study, we found that EGFR inhibitor Erlotinib had no statistical difference with the control group in blocking tumor growth. Western Blot showed downregulation of p-ERK, but upregulation of p-AKT in KYSE450 with Erlotinibl downregulation of p-ERK, but no significant change on p-AKT with Afatinib.Conclusion1. Particular ESCC can be targeted by Erlotinib, Afatinib or Alpelisib, which may be useful for the ESCC patients who have such molecular alterations.2. Erlotinib influence the growth rate but not the size of tumor (KYSE450) in mice.3. Erlotinib and Afatinib inhibit the KYSE450 cell lines by downregulating the p-ERK.