Pantoprazole sodium inhibits epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells and underlying mechanism / 中国病理生理杂志

[ ABSTRACT] AIM:To explore the inhibitory effects of pantoprazole sodium on epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells and the underlying mechanism .METHODS: Using MTT method, wound healing assay , Transwell experiment , Western blot , the differences of morphology , invasion ability , migration ability , drug sensitivity and protein expression between A 549/DDP cells and A549 cells were determined .The effect of pantoprazole so-dium on morphology , invasion ability , migration ability , drug sensitivity and protein expression in A 549/DDP cells were al-so observed.RESULTS: Compared with A549 cells, A549/DDP cells had higher invasion and migration abilities , and lower drug sensitivity , exhibited mesenchymal phenotype and activated c-Met/AKT/mTOR pathway .Pantoprazole sodium inhibited the abilities of invasion and migration , and reversed the mesenchymal phenotype , drug resistance and the c-Met/AKT/mTOR pathway activation in A549/DDP cells.Treatment with c-Met inhibitor SU11274, PI3K inhibitor LY294002 and mTOR inhibitor rapamycin had the same effects on A 549/DDP cells as that of pantoprazole sodium .CONCLUSION:Pantoprazole sodium inhibits invasion , migration, epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells by down-regulating c-Met/AKT/mTOR pathways .

Non-small cell lung cancer 95D cells co-cultured with 3D-bioprinted scaffold to construct a lung cancer model in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To fabricate an innovative scaffold for lung cancer cell culture and establish a three-dimensional lung cancer model in vitro, and to reveal the differences in biological functions of lung cancer cells under the two-dimensional and three-dimensional culture conditions.</p><p><b>METHODS</b>We chose agarose and alginate as the scaffold materials, and 3D printing technique was applied to construct cell culture scaffold. 95D cells were co-cultured with this scaffold. The differences of cell morphology, proliferation ability, protein expression, etc. in the cells cultured under 2D and 3D cultural conditions were evaluated by light microscopy using HE staining, MTT assay, scanning electron microscopy, and Western blot analysis.</p><p><b>RESULTS</b>Cells cultured in 2D wells displayed a spindle and polygonal morphology, whereas those grown in the 3D culture aggregated into spheroids, which invaded, migrated and disseminated into the surrounding scaffold. MTT assay showed that the proliferation rates of the 3D-cultured cells for 2-6 days were significantly lower than, but those cultured for 8-9 days were significantly higher than that of the 2D-cultured cells, indicating that proliferative activity of the cells grown in 2D cultures for 8-9 days was inhibited. In contrast, cells grown on 3D scaffolds still maintained a higher proliferation. The Western blot assay showed that the expression of Cdc42, p53, mTOR were significantly down-regulated in 3D scaffold-cultured group (0.529±0.103, 0.820±0.038 vs. 1.967±0.066), compared with that of the 2D-cultured group (3.063±0.139, 1.738±0.122 vs. 2.472±0.151) (P<0.05 for all), while the expression of MMP-2 was up-regulated in the 3D-cultured cells (1.110±0.029), significantly higher than that of the 2D-cultured cells (0.017±0.001) (P<0.05).</p><p><b>CONCLUSIONS</b>The cell morphology, proliferation and associated protein expression of lung cancer cells in 3D-culture systems are distinctively different as compared to those of the 2D-cultural cells. 3D-bioprinted agarose-alginate scaffold can better mimic the growth microenvironment of lung cancer in vivo and may provide a promising model for lung cancer research in vitro.</p>

Therapeutic effect of replication-deficient adenovirus carrying p16 gene on gastric cancer xenografts in nude mice / 中国肿瘤生物治疗杂志

Objective:To construct a replication-deficient adenovirus carrying p16 gene and to investigate its anti-tumor activity on human gastric cancer xenografts in nude mice.Methods:p16 cDNA was amplified by PCR and was inserted into the plasmid pSuCMV,the latter was then used to recombine the replication-deficient adenovirus AdCMV-p16 in 293 cells.Human SGC-7901 gastric cancer xenograft models were established in nude mice and were divided into 3 groups:AdCMV-p16,Ad-LacZ,and control groups.Mice in AdCMV-p16 group received intratumoral injections of 2?108 pfu/100 l AdCMV-p16(injected every other day for 5 times).Mice in control group received the same volume of virus preserving solution.The tumor volumes were measured at predefined time points.The anti-tumor effect of AdCMV-p16 was observed by p16 immunochemical study and TUNEL detection of cell apoptosis.Results:The replication-deficient adenovirus expressing p16 gene evidently inhibited the growth of human gastric cancer xenografts in nude mice(P0.05),only with a inhibition rate of 4.26%.The pathological examination showed that apoptoses were the main changes in AdCMV-p16 group,and p16 gene was found in the cancer cells.Conclusion:The replication-deficient adenovirus harboring p16 gene can recover the expression of p16 in gastric cancer cells and subsequently inhibit the growth of human gastric cancer.