Effect of andrographolide on proliferation and apoptosis of gastric cancer BGC-823 cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of andrographolide (AD) on proliferation, cell cycle and apoptosis of human gastric cells line BGC-823.</p><p><b>METHODS</b>MTT assay, flow cytometry and Annexin-V/PI double-staining flow cytometry assay were used to evaluate the effect of AD on proliferation, cell cycle and apoptosis of BGC-823 cells respectively. Optical microscope and transmission electron microscopy were used to observe the cell morphological changes.</p><p><b>RESULTS</b>A time- and concentration-dependent proliferative inhibition effect of AD was demonstrated in BGC-823 cells. AD concentration lower than 7.5 mg/L possessed weak inhibitory effect,while concentration between 15.0-60.0 mg/L possessed higher inhibitory effect. The concentration higher than 60.0 mg/L had no significant increase of inhibitory effect. IC50 of AD at 24, 48 and 72 h was (35.3±4.3), (25.5±3.5) and (18.2±2.7) mg/L respectively. Compared with the negative control group, the number of G0/G1 phase cells increased significantly (P<0.05), while the number of S and G2/M phase cells decreased after incubation with AD for 48 h, and the alteration was in a concentration-dependent manner. AD arrested BGC-823 cells at the G0/G1 phase of the cell cycle. After incubation with 7.5, 10.0 and 15.0 mg/L AD for 24 h, the early apoptotic rates of BGC-823 cells were (19.3±4.7)%, (29.4±4.1)% and (52.7±6.7)% respectively, and the late apoptotic rates were (10.8±1.8)%, (10.9±4.7)% and (14.7±4.8)% respectively. Both the early apoptotic rates and the late apoptotic rates increased significantly compared to the control group (all P<0.05),and the alteration was in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Andrographolide can inhibit BGC-823 cells proliferation, arrest BGC-823 cells in G0/G1 phase and induce apoptosis, and may be a potential traditional Chinese medicine with anti-cancer effect.</p>

Proliferative and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Andrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.</p><p><b>METHODS</b>Cell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.</p><p><b>RESULTS</b>Andrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.</p><p><b>CONCLUSIONS</b>Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.</p>

Expression of Raf kinase inhibitor protein and its significance in invasion and metastasis of hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of RKIP, p65 and pERK in hepatocellular carcinoma (HCC) and theIr correlation with invasion and metastasis of HCC.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK proteins in HCC tumor and peritumoral tissues were determined by immunohistochemistry and Western blot analysis. Statistical analysis was performed to determine the relationship between their expression and clinicopathological parameters.</p><p><b>RESULTS</b>RKIP protein expression level (RKIP/actin) was 0.579 ± 0.380 in HCCs, 1.178 ± 0.659 in peritumoral tissues and 1.115 ± 0.442 in normal liver tissues. The pERK protein level was 1.023 ± 0.478, 0.605 ± 0.367 and 0.461 ± 0.293, p65 protein level was 0.83 ± 0.376, 0.63 ± 0.337 and 0.466 ± 0.345, respectively. Immunohistochemistry analysis showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver tissues, were 22.2%, 86.0%, and 93.8%, positive rates of p65 were 73.6%, 56.0% and 37.5%, positive rates of pERK were 65.3%, 38.0% and 31.3%, respectively. Statistical analysis revealed that there was a significant difference in RKIP protein expression levels (P < 0.05), but no significant difference in RKIP mRNA expression levels (P > 0.05) among HCC tumors, peritumoral tissues and normal liver tissues. The p65-positive and pERK-positive rates were higher in tumor tissues than that in peritumoral tissues and in normal liver tissues (P < 0.05), but RKIP-positive rates were lower in tumor tissues than that in paritumoral tissues and normal liver tissues (P < 0.05). RKIP protein expression levels were significantly lower in HCCs with intrahepatic or lymphatic metastasis than that in without. The RKIP positive rates in moderately and well differentiated HCCs were significantly higher than that in poorly differentiated HCCs. There was a relationship between RKIP and pERK expressions (P = 0.04), but RKIP expression was not correlated with p65 expression in HCCs (P = 0.143).</p><p><b>CONCLUSIONS</b>Our findings indicate that the down-regulation of RKIP expression may serve as a predictive marker for HCC development, progression and metastasis, which may contribute to the elevated ERK activity. The inhibiting effect of RKIP on invasion and metastasis of liver cancer cells may be due to the down-regulation of pERK expression rather than p65 expression.</p>