ABSTRACT
Aim To evaluate the effect of ZST93 on the proliferation in human chronic myeloid leukemia(CML)cells(K562)and explore the possible mechanism.Methods MTT assay, cell growth curve and inverted microscope were used to investigate the effect of ZST93 on proliferation of K562 cells.Cell transfection and Western blot were performed to detect the autophagy, while PI staining, Annexin V-FITC/PI and flow cytometry were conducted to determine cell apoptosis and its anticancer mechanism.Results ZST93 could significantly inhibit the proliferation of K562(IC50=2.59 μmol·L-1)and induce cell cycle arrest at G1-phase in a dose- and time-dependent manner.Also, through leading to accumulation of GFP-LC3, transition into LC3- II from LC3- 1 , and decrease of p62 expression, ZST93 induced autophagy initiation and autophagic flux.Furthermore, ZST93 induced extrinsic apoptotic pathway by activating caspase-8, and further promoted the cleavage of apoptosis related proteins including caspase-9, caspase-3 and PAR P.Moreover, Z-DEYD-FMK, the specific inhibitor of caspase-3 , could dramatically reduce the apoptosis induced by ZST93.Taken together, ZST93 could effec tively inhibit CML cells, arrest eell cycle at G,-phase, induce cell apoptosis anrl initiate autophagy.Conclusions The potential mechanism may he related to the regulation of autophagy intiation/caspase-8/caspase-3 signaling pathway, which provides a new idea and theoretical basis for the treatment of CML.
ABSTRACT
Actin-like 6A (ACTL6A), also known as BAF53A, is an SWI / SNF subunit of chromatin-remodeling factors and plays an important role in regulating stem cell function. Recent studies found that ACTL6A was involved in tumor occurrence and development. However, the mechanism of ACTL6A in cisplatin resistance is still unclear. This study investigated the biological function and molecular mechanism of ACTL6A in maintaining cancer stem cell function and cisplatin resistance. First, analysis from TCGA, GEO, and GEPIA databases showed that ACTL6A expression levels in lung adenocarcinoma (LUAD) tissues and cisplatin resistant cells were dramatically higher than that in adjacent normal tissues and cisplatin sensitive cells (P < 0. 05), and ACTL6A high expression was positively associated with a poor prognosis of LUAD. Knockdown of ACTL6A enhanced cisplatin sensitivity (P < 0. 05), reduced tumor sphere (P<0. 05), inhibited cell migration (P<0. 05), and promoted cell apoptosis (P<0. 05) in A549 cells. Western blotting showed that knockdown of ACTL6A increased the protein expression of E-cadherin, and decreased the protein expression of N-cadherin, vimentin, and twist. Moreover, knockdown of ACTL6A inhibited the expression of cancer stem cell markers, including ALDH3A1, ALDH4A1, SOX2, OCT4, and Nanog. Subsequently, Hippo / YAP signaling-related proteins were analyzed by Western blotting. The results showed the expression of beta-TRCP and YAP was decreased in A549 cell with knockdown of ACTL6A. However, phosphorylation levels at S127 and S397 of YAP were increased and inhibited translocation of YAP into the nucleus for regulating related gene expression. In summary, ACTL6A maintained the stemness of lung cancer stem cells and promoted cisplatin resistance in A549 cells by inhibiting activation of the Hippo signaling pathway.
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Aim To investigate the anticancer activity of DY386 in a variety of cancer cells and the molecular mechanism of DY386 on cell cycle arrest in DU145 cells. Methods MTT assay was used to determine the inhibitory effect of DY386 on the growth of tumor cells including prostate tumor cell lines DU145, PC-3 ; glioblastoma cell line U87, non-small cell lung cancer cell lines H1975, HCC827, breast cancer cell line MCF-7, hepatoma cell line Hep3B and colon carcinoma cell line SW620. Colony formation assay and BrdU staining assay were performed to check the suppressive activity of DY386 to DU145 cell proliferation. Flow cytometry was conducted to evaluate the cell cycle distribution of DU145. Western blot was performed to detect the pro-tein level of cyclinBl, cyclinEi, CDK2, p27. Results DY386 inhibited cell growth in previous described tumor cell lines, especially in DU145 cells with half maximal inhibitory concentration (IC) value of 11.86 (imol • Flow cytometry analysis indicated that DY386 induced S phase arrest in DU145 cells. Furthermore, Western blot results revealed that DY386 decreased the expression of cyclinEi and cyclinBl and increased the expression of p27 in a dose-dependent manner. Conclusions DY386 reveals certain antitumor effect, and its mechanism may be related to inhibiting cell proliferation by blocking cell cycle.
ABSTRACT
Objective To analyze the relationship between monthly average air temperature and monthly mortality rate among the elderly.Methods The death cause surveillance data between 2011 and 2013 of Yongkang City were used,and the monthly air temperature data was from Statistical Yearbooks published by Bureau of Statistics,and the population data was from the Yongkang public security bureau during this period.The scatter plot of the monthly average temperature and the mortality rate of the elderly were made.According to different causes of death,a linear regression analysis were used to analyze the relationship between the two variables.(The monthly mortality rate was the dependent variable and the monthly average temperature was the independent variable).Results There were negative correlation between the monthly air temperature and the mortality rate caused by circulatory disease(r =-0.884,P <0.001).There were negative correlation between the monthly air temperature and the mortality rate caused by respiratory disease.When the monthly air temperature was ≤15 ℃,and regression mode was Y = -6.399 X +186.813(Adjusted R2 =0.247).No obvious relationship between the monthly air temperature and the mortality rate caused by malignant tumor was observed(R2linear =0.006).Conclusion There is a certain relationship between monthly average air temperature and monthly mortality rate among the elderly. Health -care and nursing of the elderly should be strengthened when the temperature is low,especially for those aged over 80 years.