• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.625-631
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• 2012

In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micromorphological changes, and expression of SphK1, P-gp, NF-${\kappa}B$, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-${\kappa}B$ and Bcl-2 was decreased significantly,while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-${\kappa}B$(r=0.723, P<0.01), NF-${\kappa}B$ and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-${\kappa}B$.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4685-4688
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• 2013

We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were ($21.07{\pm}2.12$)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to ($30.16{\pm}3.54$)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5619-5625
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• 2012

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.