Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (9): 6-10.doi: 10.6040/j.issn.1671-7554.0.2018.535

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Recombinant human vascular endostatin enhances antitumour activity of EGFR-TKIs for lung cancer

SHI Shuyuan1, GUAN Zhiyu1, SUN Daqiang2   

  1. 1. Department of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211, China;
    2. Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300051, China
  • Published:2022-09-27

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Abstract: Objective To study the inhibitory effect of recombinant human vascular endostatin(endostar)combined with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), erlotinib, on the resistant cell lines of EGFR-TKIs H1975(with L858R and T790M)in vitro and in vivo. Methods The cell activity of H1975 cell line was detected, and the absorbance values of erlotinib, endostar and erlotinib + endostar were determined. The xenograft tumor model of H1975 lung cancer cell line was established, and the nude mice were randomly divided into 4 groups(control group, erlotinib group, endostar group and combined medication group), 6 in each group. The tumor diameter was measured once every 3 days since the administration of the drug, and all the experimental mice were executed 2 weeks later. The tumors were taken out, measured and photographed. Results Cell experiments in vitro showed that, erlotinib had a statistically significant inhibitory effect on H1975 cell proliferation(P=0.043), while endostar had no statistically significant inhibitory effect on H1975 cell proliferation(P=0.261). The effect of erlotinib + endostar coincided with erlotinib. The animal experiments in vivo showed that, endostar could not inhibit the tumor cell growth(P= 山 东 大 学 学 报 (医 学 版)56卷9期 -石树远,等.重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用 \=-0.112), and erlotinib could inhibit the tumor cell growth (P=0.018). Meanwhile, the two drugs exhibited a synergistic effect(P=0.048). Further pairwise comparison showed statistically significant differences between the combined medication group and control group/erlotinib group(P=0.046, P=0.023). Conclusion Endostar combined with erlotinib can enhance antitumour activity of erlotinib for lung cancer and reverse the T790M-related drug resistance. Endostar combined with erlotinib has a promising application prospect for patients with EGFR-TKIs resistance.

Key words: Recombinant human vascular endostatin, Epidermal growth factor receptor tyrosine kinase inhibitor, Resistant

CLC Number: 

  • R734.2
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