ABSTRACT
Objective To investigate the effect of Anlotinib on proliferation and apoptosis in non-small cell lung cancer(NSCLC)cells and its molecular mechanism.Methods Non-small cell lung cancer cell lines A549 and H1299 were incubated with Anlotinib,miR-16-5p agonist and/or PD-1 overexpression vector respectively.CCK-8 assay and EDU assay were applied to detect the proliferation.Flow cytometry was performed to detect the cell apop-tosis.The relative expression of miR-16-5 p in A549 and H1299 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).The relative protein expression of PD-1 in A549 and H1299 was detected by Western blot assay.The interaction between miR-16-5p and PD-1 was determined by dual luciferase reporter assay.Finally,A549 cell xenograft model was established to assess the effect of Anlotinib on tumor growth in vivo.Results Anlotinib significantly increased miR-16-5p expression and decreased PD-1 expression in A549 cells and H1299 cells,inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P＜0.05).The highly-expressed miR-16-5p inhibited proliferation and promoted cell apoptosis(P＜0.05).Also,miR-16-5p targeted at PD-1 and negatively regulated PD-1 expression.Knockdown of PD-1 inhibited proliferation and pro-moted cell apoptosis(P＜0.05).PD-1 over-expression reversed the Anlotinib-mediated pro-proliferation and anti-apoptosis of miR-16-5p in A549 cells and H1299 cells(P＜0.05).Anlotinib significantly reduced tumor growth in vivo(P＜0.05).Conclusions Anlotinib may inhibit cell proliferation,anti-apoptosis,and reduce tumor growth for NSCLC,which is involved in miR-16-5p/PD-1 axis.
ABSTRACT
Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.
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Objective To investigate the expression and clinicopathological significance of CXCR4 and HIF-1α protein in esophageal squamous cell carcinoma tissue and explore their correlation.Methods The expression of CXCR4 and HIF-1α protein were assessed by immunohistochemistry SP method in 56 cases with esophageal squamous cell carcinoma and in 20 cases with surrounded normal tissue.Results The expressions of CXCR4 and HIF-lα in esophageal squamous cell carcinoma were significantly higher than those in normal tissues[62.50 ％ (35/56) vs 10.00 ％ (2/20); 57.14 ％ (32/56) vs 0(0/20)](x2=16.259,19.740,P ＜0.01).The expression of CXCR4 and HIF-1α were both correlated with invasion depth (x2 =4.736,7.665,P ＜0.05) and lymph node metastasis ( x2 =7.207,6.389,P ＜0.05),and had no correlation with cancer cell differentiation.The expressions of CXCR4 and HIF-lα in esophageal squamous cell carcinoma were positively correlated (r =0.298,P ＜0.05).Conclusion CXCR4 and HIF-1α are highly expressed in esophageal squamous cell carcinoma.The two have a close relation to esophageal squamous cell carcinoma growth,invasion and metastasis.