scholarly journals Up-regulated Wnt1-inducible signaling pathway protein 1 correlates with poor prognosis and drug resistance by reducing DNA repair in gastric cancer

2019 ◽  
Vol 25 (38) ◽  
pp. 5814-5825 ◽  
Author(s):  
Li-Hua Zhang ◽  
Yan Wang ◽  
Qian-Qian Fan ◽  
Yan-Kui Liu ◽  
Long-Hai Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Dna Repair ◽  
Signaling Pathway ◽  
Poor Prognosis

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Dongmei Zhan ◽  
Tengyang Ni ◽  
Haibo Wang ◽  
Mengying Lv ◽  
Masataka Sunagawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Resistance Index ◽  
Mtor Signaling ◽  
Control Group ◽  
Human Gastric Cancer ◽  
Cancer Resistance ◽  
Mtor Signaling Pathway ◽  
Expression Levels

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

Babao dan promotes apoptosis of cisplatin (DDP)-resistant gastric cancer cell line SGC-7901/DDP by inducing autophagy through PI3K/AKT/mTOR pathway modulation

2020 ◽  
Author(s):  
Jinyan Zhao ◽  
Weilan Lan ◽  
Jun Peng ◽  
Bin Guan ◽  
Jie Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Line ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Pathway ◽  
Cell Protein ◽  
Drug Resistant ◽  
Gastric Cancer Cells

Abstract Background: Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Babao dan (BBD) is a classical and famous traditional Chinese patent medicine, which has been reported to has anti-gastric cancer activity. However, the roles and molecular mechanisms of the reversal of MDR of gastric cancer by BBD have not been well described until now. Methods: SGC-7901 and SGC-7901/DDP cells were used in this study, and drug resistance and evaluation of the reversal effect of BBD was determined using MTT assays in SGC7901/DDP cells. Doxorubicin (DOX) and Rhodamin123 (Rho123) staining was performed to assess BBD effects on drug accumulation and efflux of drug-resistant gastric cancer cells. Cell apoptosis was directly assessed using DAPI staining. Apoptotic and dead cells were detected by flow cytometry after staining with Annexin V-FITC and propidium iodide (PI). Cyto-ID assays were performed to examine cellular autophagy. Changes in cell protein expression of ABCB1, ABCC1, ABCG2, Bax, Bcl-2, caspase-3, cleaved-caspase-3, LC3, p62, Beclin1 and the PI3K/AKT/mTOR pathway were detected by Western blot. Inhibition of autophagy with 3-MA, chloroquine (CQ) and PI3K antagonist (LY294002) or agonist (740Y-P) , uncovered a role for the potentially downregulated signaling pathway, PI3K/AKT/mTOR.Results: The SGC7901/DDP cell line exhibited multi-drug resistance to DDP, DOX and 5-fluorouracil (5-FU) and the drug resistant index (RI) of DDP, DOX and 5-FU were 1.86, 1.50 and 47.70, respectively. BBD reversed the MDR of SGC7901/DDP cells by increasingDOX accumulation, reducing Rh123 efflux and down-regulating the expression of ABCB1, ABCC1, ABCG2. Furthermore, BBD induced apoptosis in SGC7901/DDP cells through regulating caspase-3, cleaved-caspase-3, Bax and Bcl-2. Moreover, BBD induced autophagy in DDP-resistant gastric cancer cells via regulating p62, LC3 and Beclin1. Pathway analyses suggested BBD may inhibit PI3K/AKT/mTOR pathway activity and subsequent autophagy induction. Conclusions: BBD may reverse the MDR of gastric cancer cells, and promote autophagic death via inactivation of the PI3K/AKT/mTOR signaling pathway.

scholarly journals MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway

2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Liwei An ◽  
Pingping Nie ◽  
Min Chen ◽  
Yang Tang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Human Gastric Cancer ◽  
Hippo Signaling ◽  
Wild Type ◽  
Hippo Signaling Pathway ◽  
Phosphorylation Level ◽  
Signaling Axis ◽  
Importin Α

Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4–YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin α, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4–YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4–YAP signaling axis essential for suppressing gastric tumorigenesis.

scholarly journals Upregulated β-arrestin1 predicts poor prognosis and promotes metastasis via AKT/ERK signaling pathway in gastric cancer

2020 ◽  
Vol 216 (12) ◽  
pp. 153262
Author(s):  
Tingjuan Xu ◽  
Guodong Shen ◽  
Min Cheng ◽  
Xinchun Wu ◽  
Yayuan Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Erk Signaling

scholarly journals lncRNA ROR Promotes Gastric Cancer Drug Resistance

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090469 ◽  
Author(s):  
Shuai Wang ◽  
Wujun Chen ◽  
Hualong Yu ◽  
Zhengming Song ◽  
Qian Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Cancer Drug ◽  
Gastric Cancer Cells ◽  
Mrp1 Expression

Objective: Gastric cancer is one of the most common malignant tumors worldwide, and for resectable tumors, the most effective treatment is surgery with chemotherapy in neoadjuvant or adjuvant setting. However, the majority of patients fail to achieve the ideal initial response and/or develop resistance to chemotherapy. It was reported that long noncoding RNA regulator of reprogramming (ROR) is highly associated with the progression of gastric cancer. However, the role ROR in multidrug resistance (MDR) remains unclear. Methods: The messenger RNA levels of 63 specimens of patients with gastric cancer were determined by real-time polymerase chain reaction analysis and were correlated with drug resistance and survival of patients. To determine the cellular functions of ROR, we generated gastric cancer MDR cells. The effect of ROR depletion on multidrug resistance-associated protein 1 (MRP1) expression and cell apoptosis were examined by immunoblotting analyses, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry. Results: We found that ROR expression levels are positively associated with increased MDR and poor prognosis of patients with gastric cancer. Regulator of reprogramming expression is increased in gastric cancer cells resistant to adriamycin (ADR) and vincristine (VCR). Depletion of ROR reduced MRP1 expression and increased apoptosis of drug-resistant gastric cancer cells in response to ADR and VCR treatment. Conclusions: We demonstrated that ROR expression promotes MRP1 expression and MDR of gastric cancer cells and is correlated with increased MDR and poor prognosis of patients with gastric cancer. Our finding highlighted the potential of targeting ROR to improve the efficacy of chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document