The role and research progress of PLOD2 in tumor metastasis / 医学研究生学报

Tumor invasion and metastasis are the main factors leading to poor prognosis of cancer patients.In recent years, studies have found that collagen fiber remodeling in extracellular matrix(ECM) can promote tumor invasion and metastasis . Lysine hydroxylase 2(PLOD2) is the only lysine hydroxylase that changes the pattern of collagen fiber cross-linking and remodeling. It is highly expressed in many tumors and is closely related to tumor invasion and metastasis,Therefore, in-depth study of the role and mechanism of PLOD2 in tumor metastasis is of great scientific value for judging tumor prognosis and preventing tumor invasion and metastasis.This article reviews the recent advances in the role and potential mechanisms of PLOD2 in tumor invasion and metastasis.

Effect of bufalin combined gefitinib on lung cancer H1975 cells and its mechanisms research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of bufalin combined Gefitinib on lung cancer H1975 cells, and to explore its potential mechanisms for anti-tumor.</p><p><b>METHODS</b>The cytostatic effects of bufalin (1 -100 nmol/L), gefitinib (0.1-20 micromol/L), and bufalin plus gefitinib on H1975 cells were evaluated by MTT assay. Their effects on apoptosis of H1975 cells were determined by flow cytometry (FCM). Their effects on expressions of epidermal growth factor receptor (EGFR) and Met signal pathway related proteins in H1975 cells were detected by Western blot.</p><p><b>RESULTS</b>Results of MTT assay showed that gefitinib over 5 micromol/L could inhibit H1975 cells. But combined therapy of bufalin and gefitinib could potently inhibit the growth of H1975 cells. Results of FCM showed the apoptotic rate was 61.64% +/- 5.61% in the bufalin plus gefitinib group, obviously higher than that of the bufalin group (18.34% +/- 3.42%) and the gefitinib group (7.32% +/- 1.08%), showing statistical difference (P < 0.01). Results of Western blot showed the protein expressions of p-EGFR, p-Met, p-Akt, and p-mTOR in H1975 cells could be markedly down-regulated by bufalin plus gefitinib.</p><p><b>CONCLUSIONS</b>Combination of bufalin and gefitinib potently inhibited the growth of H1975 cells, and induced cell apoptosis. The potential mechanism for anti-tumor might be involved in blocking EGFR-PI3k/Akt pathway.</p>

Bufalin reverses resistance to gefitinib in xenografts of lung adenocarcinoma H 1975 cells in nude mice / 肿瘤

Objective: To investigate the effect of bufalin in combination with gefitinib on the growth of xenotransplants of lung adenocarcinoma H 1975 cells in nude mice, and to explore its possible mechanism. Methods: Forty nude mice bearing subcutaneous xenotransplants of lung adenocarcinoma H 1975 cells were randomly divided into four groups (in each group there were 10 nude mice): control group (no treatment), gefitinib-treated group, bufalin-treated group and bufalin in combination with gefitinib-treated group. Each group received corresponding intervention for 3 weeks. Tumor inhibitory rate was calculated. Apoptotic rate was measured by TUNEL staining method. The expression levels of EGFR-PI3K (epidermal growth factor receptor-phosphoinositide 3-kinase)/Akt signaling pathway-related proteins in xenografts were detected by Western blotting. Results: The tumor inhibitory rates of the control, gefitinib-treated, bufalin-treated and bufalin in combination with gefitinib-treated groups were 0%, 16.14%, 33.48% and 60.39%, respectively. The apoptotic rate of bufalin in combination with gefitinib-treated group was (75.8±3.16)%, which was significantly higher than those of the control group [(13.11 ± 1.60)%], gefitinib-treated group [(15.48±0.43)%] and bufalin-treated group [(45.09±3.81)%] (P < 0.01). The expression levels of phospho-EGFR, phospho-PI3K and phospho-Akt proteins were significantly reduced in group of bufalin in combination with gefitinib (P < 0.01). Conclusion: Bufalin in combination with gefitinib may block the EGFR-PI3K/Akt pathway to reverse the resistance to gefitinib in xenografts of lung adenocarcinoma H 1975 cells in nude mice. Copyright © 2013 by TUMOR.

Tumor microenvironment elicits primary resistance to afatinib through HGF secretion / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the effects of hepatocyte growth factor (HGF) derived from tumor microenvironment and/or afatinib on the growth of human lung adenocarcinoma H1975 cells and explore the potential mechanisms by which HGF induces primary resistance to afatinib.</p><p><b>METHODS</b>The effects of HGF, TGF-α and afatinib on the growth of H1975 cells were evaluated by MTT assay. The HGF concentrations of normal human fetal lung fibroblasts MRC-5 cells and human lung adenocarcinoma H1975 cells co-cultured or separately cultured were determined by ELISA assay. Western blot was used to detect the expressions of EGFR and Met signal pathway-related proteins and epithelial-mesenchymal transition (EMT) markers in H1975 cells treated with HGF and/or afatinib.</p><p><b>RESULTS</b>The MTT assay showed that H1975 cells were hyposensitive to afatinib in the presence of HGF. The ELISA assay showed that HGF production by H1975 cells was less than 0.1 ng/2.0×10(6) cells, but HGF production by MRC-5 cells was (151.37 ± 2.07)ng/2.0×10(6) cells incubated for 48 h. When H1975 cells and MRC-5 cells were co-cultured for 72 h, the concentration of HGF in the culture supernatant was (61.13 ± 16.21)ng/ml. In the presence of HGF, the expression of p-Met, p-Akt and p-ERK proteins in the H1975 cells was markedly up-regulated. afatinib inhibited p-EGFR, but did not affect the expression of p-Met, p-Akt and p-ERK proteins. In the presence of afatinib, HGF up-regulated the expression of vimentin and down-regulated the expression of E-cadherin.</p><p><b>CONCLUSIONS</b>HGF secreted by stromal cells in the tumor micro-environment may confer resistance to afatinib in H1975 cells by activation of the Met/PI3K/Akt and Met/MAPK/ERK signaling pathways, and is involved in the epithelial-mesenchymal transition process.</p>