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2018年浙江省男科学、泌尿外科学学术年会

作者：高建国湖州市第一人民医院

目的:The resistance of renal cell carcinoma to available chemo-and radio-therapy approaches is a challenge to *** present study investigates the effect of retinamide on renal carcinoma cells.方法:Cell proliferation was analysed using MTT,apoptosis and cell cycle arrest by flow cytometry.结果:In RCCs treatment with 4HPR caused significant inhibition of viability at 30μM *** of 786-O and OS-RC-2 cell lines with 4HPR reduced the rate of colony *** was found that 4HPR treatment enhanced p38 and JNK activation in 786-O cells at 48 *** blot assay showed that p38 and JNK activation by 4HPR was inhibited on pre-treatment with SB203580 and SP600125,respectively in 786-O *** of786-O cell viability by 4HPR treatment was also prevented significantly (p<0.05) by sb203580 and sp600125 ***,inhibitors of p38 and JNK also reversed the effect of 4HPR on Bax and Bcl-2 expression in786-O cells.结论:Thus 4HPR treatment inhibits growth of renal cancer cells through MAPK signaling pathway activation.4HPR,therefore can be used as new treatment approach for the renal cancer.

关键词： hydroxyphenyl inhibits cell migration and promotes autophagy via MAPK p38 pathway in renal cell carcinoma retinamide HPR

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Induction of Mitochondrial Pathways and Endoplasmic Reticulum Stress for Increasing Apoptosis in Ectopic and Orthotopic Neuroblastoma Xenografts

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Journal of Cancer Therapy 2011年第2期2卷 77-90页

作者： Surajit Karmakar Subhasree Roy Choudhury Naren Lal Banik Swapan Kumar Ray Department of Pathology Microbiology and Immunology University of South Carolina School of Medicine Columbia South Carolina USA.

Cancers are characterized by deregulation of multiple signaling pathways and thus monotherapies are hardly effective. Neuroblastoma, which often occurs in adrenal glands, is the most common childhood malignancy. Malignant neuroblastoma resists traditional treatments and further studies are needed for effective therapeutic interventions. We evaluated synergistic efficacy of N-(4-hydroxyphenyl) retinamide (4-HPR) and genistein (GST) for induction of apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells in culture and activation of multiple pathways for increasing apoptosis in ectopic and orthotopic neuroblastoma xenografts in nude mice. Combination of 4-HPR and GST synergistically reduced cell viability, caused subG1 accumulation, increased caspase-3 activity for apoptosis in vitro and reduced tumor growth in vivo. Western blotting indicated that combination therapy down regulated Id2 to induce differentiation, increased pro-apoptotic Bax and decreased anti-apoptotic Bcl-2 leading to an increase in Bax:Bcl-2 ratio, increased mitochondrial Bax level, caused mitochondrial release of Smac/Diablo, down regulation of the baculovirus inhibitor-of-apoptosis repeat containing (BIRC) proteins such as BIRC-2 and BIRC-3, and activation of calpain and caspase-3 in SH-SY5Y xenografts. Accumulation of apoptosis-inducing-factor (AIF) in cytosol and increase in caspase-4 activation suggested involvement of mitochondrial pathway and endoplasmic reticulum (ER) stress, respectively, for apoptosis in SH-SY5Y xenografts. In situ immunofluorescent labelings of SH-SY5Y and SK-N-BE2 xenograft sections showed overexpression of calpain, caspase-12, and caspase-3, and AIF, suggesting induction of mitochondrial caspase-dependent and caspase-independent pathways for apoptosis. Collectively, synergistic effects of 4-HPR and GST induced mitochondrial pathways and also ER stress for increasing apoptosis in ectopic and orthotopic neuroblastoma xenografts in nude mice.

关键词： Apoptosis Endoplasmic Reticulum Stress Genistein N-(4-Hydroxyphenyl) retinamide Neuroblastoma

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