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Aim To set up leukemic K562/ADM cells with stable tolerance to 15 fimol • L_1 ADM induced in vitro by long-term and continuous stepwise increment of adriamycin (ADM) concentration, to observe the sensitivity to other chemotherapy drugs and the relationship between autophagy and drug resistance.Methods MTT assay was used to detect the sensitivity of cells to chemotherapy drugs.The morphological changes of autophagy were observed by transmission electron microscope and fluorescence microscopy.Cell apoptosis analysis was performed using Annexin-V/PI double staining and flow cytometry ( FCM ).The expressions of autophagy and drug resistance associated proteins were tested by Western blot.Results K562/ADM cells were cross-resistance to the other chemotherapeu-tics besides adriamyciri, such as pirarubicin, daunoru- bicin, 5-flurouracil, vincristine but not arsenic triox- ide.The number of autophagosomes, the fluorescence intensity of monodansylcadaverine (MDC) and the expression of LC3-H ,Beclin-l in K562/ADM cells were significantly higher than those in K562 cells.The inhibition of autophagy by 3-MA significantly increased the sensitivity of K562/ADM cells to ADM, and 3-MA also effectively inhibited the expressions of drug resistance related proteins P-gp, MRP1 and BCRP in K562/ADM cells.Conclusions The K562/ADM cells resistant to adriamycin occur multidrug resistance, and the drug resistanceis closely related to the level of autophagy.
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Aim To research the cross-talk and conversion between macroautophagy and chaperone-media-ted autophagy ( CMA) in cultured Burkitt lymphoma Raji cells induced by starvation. Methods The autophagic vacuoles were observed by fluorescence microscopy and confocal laser-scanning microscopy with monodansylcadaverine staining. The expression of autophagy associated-proteins were determined by West-em blot. Results Both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of near baseline. With starvation persisted, CM A progressively increased along with the decline of macroautoph- A gy. Conclusions Macroautophagy and CMA are maximally activated during different stages of starvation. Activation of these two pathways is often sequential. The sequential switch from macroautophagy to CMA might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular changes, maintaining their own growth and proliferation.
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<p><b>OBJECTIVE</b>To investigate the HLA-A, B and DRB1 allele polymorphism of the Han race population in Lanzhou area.</p><p><b>METHODS</b>Polymerase chain reaction-sequence specific primer was used to detect HLA-A, B and DRB1 alleles in 200 unrelated healthy Han individuals from Lanzhou region, Northwest China, and the results were compared with those of Han populations in North, South and Northwest China, and Hui, Uigur and Tibetan population in China.</p><p><b>RESULTS</b>Fourteen of alleles were detected and identified for HLA-A; 32 for HLA-B; and 13 for HLA-DRB1. HLA- A*01, A*02,A*11,A*24, A*30, A*31, A*33; HLA- B*13, B*15, B*40, B*44, B*46, B*51, B*58, B*60; HLA- DRB1*04,. DRB1*07, DRB1*08, DRB1*09, DRB1*11, DRB1*12, DRB1*14 and DRB1*15 were the most common alleles. The frequencies of HLA-A, B and DRB1 genes of Lanzhou Han race were close to that of North China Hans and Hui population in Northwest China, and a little different to that of South China Hans. The HLA-DRB1 alleles were significantly different to those of Uigur and Tibetan race population of China.</p><p><b>CONCLUSION</b>The allelic polymorphism of HLA-A,B and DRB1 loci of Han race population in Lanzhou area was between North and South Han race of China, close to Northwest China Hui, and markedly different to Northwest China Uigur and Tibetan race populations.</p>