Search

Introduction Gastric cancer is the third leading cause of death in cancers worldwide and it had considerably high mortality in China (Orditura 2014). Although compounds of platinum combined with other [...], Autophagy plays critical roles in tumorigenesis, while the effects of autophagy on chemoresistance of cancer cells had great disparity. This study aims to explore the impacts of autophagy on the sensitivity and resistance of gastric cancer cells to cisplatin (DDP). We firstly demonstrated that there was stronger autophagy activity in gastric cancer SGC-7901 cells than that in DDP-resisting SGC-7901/DDP cells. Then, we discovered that inhibiting autophagy by chloroquine (CQ) significantly enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP to SGC-7901 and SGC-7901/DDP cells. Moreover, CQ could partially reverse the resistance of SGC-7901/DDP cells to DDP in a concentration-dependent manner. However, the autophagy inducer everolimus (RAD001) had no obvious effects on the sensitivity of gastric cells to DDP. Mechanistically, we demonstrated that CQ might enhance the sensitivity of SGC-7901cells and improve the resistance of SGC-7901/DDP cells to DDP through inhibiting the mTORC1 pathway, especially to SGC-7901/DDP cells. Additionally, we found interfering Beclin-1 using Beclin-1 shRNA also enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP on gastric cancer cells by inhibiting phosphorylation of Akt. Our study shows that inhibiting autophagy could improve the chemoresistance and enhanced sensitivity of gastric cancer cells to DDP and provide a rationale for the administration of cisplatin combined with CQ for treating patients with gastric cancer. Key words: autophagy, chemoresistance, cisplatin, gastric cancer. L'autophagie joue un role crucial dans le tumorogenese, tandis que les effets de l'autophagie sur la chimioresistance des cellules cancereuses sont tres variables. Cette etude visait a explorer l'incidence de l'autophagie sur la sensibilite et la resistance des cellules gastriques cancereuses au cisplatine (DDP). Nous avons d'abord montre que l'activite autophagique etait plus importante dans les cellules gastriques SGC-7901 que dans les cellules SGC- 7901/DDP resistantes au cisplatine. Ensuite, nous avons observe qu'en inhibant l'autophagie, la chloroquine (CQ) entrainait une augmentation notable des effets inhibiteurs de la proliferation et inducteurs de l'apoptose du DDP envers les cellules SGC-7901 et SGC-7901/DDP. En outre, la CQ pouvait entrainer une inversion partielle de la resistance des cellules SGC-7901/DDP au DDP de maniere dependante de la concentration. Cependant, l'everolimus (RAD001), un inducteur de l'autophagie, n'avait aucun effet manifeste sur la sensibilite des cellules gastriques au DDP. Au point de vue des modes d'action, nous avons montre que la CQpourrait entrainer une augmentation de la sensibilite des cellules SGC-7901 et une amelioration de la resistance des cellules SGC- 7901/DDP au DDP par l'intermediaire de l'inhibition de la voie de signalisation de mTORC1, en particulier envers les cellules SGC- 7901/DDP. A l'aide de l'ARNsh de becline-1, nous avons de plus observe qu'en interferant avec la becline-1, on obtenait une augmentation des effets d'inhibition de la proliferation et d'induction de l'apoptose du DDP sur les cellules gastriques cancereuses par l'intermediaire de l'inhibition de la phosphorylation de l'Akt. Notre etude expose que l'inhibition de l'autophagie pourrait entrainer une amelioration de la chimioresistance et une augmentation de la sensibilite des cellules gastriques cancereuses au DDP, et fournit une rationnelle en faveur de l'administration de cisplatine en association avec de la CQ pour le traitement des patients atteints de cancer gastrique. Mots-des : autophagie, chimioresistance, cisplatine, cancer gastrique.

Nowadays, a variety of coatings such as Ti-Al-N and TiN have been proposed in titanium machining, but few results on fabrication of bulk Ti/AlN composites were reported. Here, we prepared bulk Ti-60 wt%AlN composites via vacuum hot-press sintering at 1250°C-1450°C under an applied pressure of 30 MPa for 1 h. With sintering temperature increasing, the mechanical properties of Ti/AlN composites improved and achieved the maximum values when the sintering temperature is 1450°C. SEM detected the multilamellar grains which are confirmed as Ti-Al-N solid solution by XRD and EDS. Finally, microstructure evolution and phase transformation of Ti/AlN composites were illustrated that Al and N atoms diffuse across the grain boundary and react with Ti atoms to form TiN phase and multilamellar Ti-Al-N solid solution. This work is interesting for producing high strength and toughens metal/ceramic composites. [ABSTRACT FROM AUTHOR]

Dysregulation of microRNA contributes to multiple tumorigenic processes. Although downregulation of miR-199a-3p has been shown in many cancers, its effects on esophageal squamous cell carcinoma (ESCC) and the regulatory mechanism are still obscure. Here, we aim to evaluate the biological function and underlying mechanisms of miR-199a-3p in ESCC as well as its value to clinical treatment of ESCC. We first analyzed expression of miR-199a-3p in esophageal cancer by bioinformatic analysis and found that there were different opinions about expression of miR-199a-3p in esophageal cancer, and the following qRT-PCR assay demonstrated which was markedly downregulated in ESCC cells. Next, we increased the expression of miR-199a-3p in ESCC cells using miR-199a-3p mimics and demonstrated that overexpression of miR-199a-3p significantly inhibited cell proliferation, migration and invasion, as well as induced cell cycle retard and promoted apoptosis in ESCC. Furthermore, we explored the functional targets of miR-199a-3p and identified that overexpression of miR-199a-3p inhibited mTOR/p70S6K pathway, but stimulated PI3K/Akt pathway. Finally, we demonstrated that overexpression of miR-199a-3p enhanced proliferation-inhibiting effects of MK2206, an inhibitor of Akt, to ESCC cells, which might be related that MK2206 eliminated the activation of miR-199a-3p to p-Akt. These findings discover that miR-199a-3p might participate in the carcinogenesis process of ESCC, which provides a new insight for treatment of ESCC., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore the differences in sensitivity to rapamycin of five esophageal squamous cell carcinoma cell lines with different differentiation and the changes of sensitivity of the cells after siRNA-interfered expression of p70S6K., Methods: Effects of rapamycin on proliferation of ESCC cell lines with different differentiation, EC9706, TE-1, Eca109, KYSE790 and KYSE450 cells, were investigated using cell counting kit 8 (CCK-8) assay, and according to the above results, the EC9706 cells non-sensitive to rapamycin were chosen to be transfected with p70S6K-siRNA. The changes in sensitivity of cells to rapamycin were measured in vitro and in vivo using CCK-8 kit, flow cytometry and tumor formation in nude mice., Results: CCK-8 results showed that all the five cell line cells were sensitive to low concentration of rapamycin (<100 nmol/L), but TE-1 and EC9706 cells, which were with poor differentiation, showed resistance to high concentration of rapamycin. After EC9706 cells were treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and p70S6K-siRNA, the proliferation rates of EC9706 cells were (48.67 ± 1.68)%, (15.45 ± 1.54)%, (14.00 ± 0.91)%, (10.97 ± 0.72)% and (2.70 ± 0.32)%, respectively, and were significantly lower than that of cells treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and control siRNA [(74.53 ± 1.71)%, (68.27 ± 1.35)%, (71.74 ± 2.44)%, (76.23 ± 1.02)% and (80.21 ± 2.77)%] (P<0.05 for all). The results of flow cytometry showed that the ratios of cells in G1 phase of the p70S6K-siRNA, rapamycin and p70S6K-siRNA+ rapamycin groups were (53.82 ± 1.78)%, (57.87 ± 4.01)% and (73.73 ± 3.68)%, respectively, significantly higher than that in the control group (46.09 ± 2.31)% (P<0.05 for all). The results of tumor formation test in vivo showed that the inhibitory effect of rapamycin on tumor growth was stronger after the cells were transfected with p70S6K-siRNA, and the inhibition rate was 96.5%., Conclusion: ESCC cells with different differentiation have different sensitivity to rapamycin, and p70S6K-siRNA can improve the sensitivity of cells to rapamycin in vitro and in vivo.