IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling

Niu, Xiulong; Liu, Wenxing; Wang, Yue; Liu, Xiaomei; Zhang, Hongjian; Li, Zhijun; Hong-zhao, LI; Iwakura, Yoichiro; Deng, Weimin

doi:10.18632/oncotarget.10655

Cited by 6 publications

(6 citation statements)

References 44 publications

(58 reference statements)

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“…In our RNAi screen, 14 out of 55 (25.5%) of the candidates exhibited synergy in cell killing when combined with cisplatin at corresponding cisplatin IC 50 dose (Figure 1A ), some of which were reported to contribute to cisplatin resistance when overexpressed, such as STAT3 , MDR1 and ATP7A [ 22 , 23 ]. To validate the RNAi result, the human breast cancer cell lines T47D, MDA-MB-231 and MCF7, as well as the BRCA1 -mutant mouse breast cancer cell line 69, were treated with cisplatin alone or in combination with ATP7A siRNA respectively.…”

Section: Resultsmentioning

confidence: 99%

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

Chisholm

Wang²,

Wong³

et al. 2016

Oncotarget

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Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target. ATP7A is a copper ATPase transporter responsible for intercellular movement and sequestering of cisplatin. Pharmaceutical replacement for ATP7A by ammonium tetrathiomolybdate (TM) enhanced cisplatin treatment in breast cancer cells. Allograft and xenograft models in athymic nude mice treated with cisplatin/TM exhibited retarded tumor growth, reduced accumulation of cancer stem cells and decreased cell proliferation as compared to mono-treatment with cisplatin or TM. Cisplatin/TM treatment of cisplatin-resistant tumors reduced ATP7A protein levels, attenuated cisplatin sequestering by ATP7A, increased nuclear availability of cisplatin, and subsequently enhanced DNA damage and apoptosis. Microarray analysis of gene ontology pathways that responded uniquely to cisplatin/TM double treatment depicted changes in cell cycle regulation, specifically in the G1/S transition. These findings offer the potential to combat platinum-resistant tumors and sensitize patients to conventional breast cancer treatment by identifying and targeting the resistant tumors' unique molecular adaptations.

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Section: Resultsmentioning

confidence: 99%

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

Chisholm

Wang²,

Wong³

et al. 2016

Oncotarget

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show abstract

“…MDR1 plays an important role in the development of drug resistance in cells, according to actively effluxes a wide array of anticancer drugs, including cisplatin and paclitaxel [ 33 ]. ERCC1 expression levels determined the sensitivity of cells to Pt in part [ 34 ], and LRP expression was associated with resistance to anti-cancer drugs including cisplatin, carboplatin, doxorubicin, etoposide and paclitaxel in vitro [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Enhanced antitumor efficacy of cisplatin for treating ovarian cancer in vitro and in vivo via transferrin binding

et al. 2017

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Cisplatin is a widely used anticancer drug, while non-targeted delivery, development of drug resistance, and serious side effects significantly limit its clinical use. In order to improve the tumor-targeting properties of cisplatin, transferrin (Tf) was employed as a carrier to transfer cisplatin into cancer cells via transferrin receptor 1 (TfR1) mediated endocytosis. The binding ability of cisplatin and Tf could be improved by pretreating Tf with 10% ethanol, and the binding number of cisplatin for each Tf molecule could reach to 40 without structural or functional impairment of Tf. The Tf-cisplatin complex could be delivered into human ovarian carcinoma cells high efficiently. In tumor-bearing nude-mice model, the Tf-cisplatin complex inhibited tumor growth in vivo more effectively than free cisplatin, with less toxicity in other tissues. Tumor targeting efficiency of the Tf-cisplatin complex was supported by in vivo and ex vivo imaging and platinum residues detected in each ex vivo organ. These data suggested that Tf-cisplatin was more effective and less drug-resistance than cisplatin, with targeting to tumor cells. Therefore, Tf-mediated delivery of cisplatin is a potential strategy for targeted delivery into tumor cells.

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“…In the primary lesions, epithelial ovarian carcinoma is the most common malignant ovarian tumor (70% of all ovarian malignancies), besides, the stromal tumors of the ovary, germ-cell tumors, sex-cord stromal tumors, and other more rare types are also included. [ 3 ] Unfortunately, early ovarian cancer is minimal, nonspecific, or even asymptomatic due to its anatomy features, [ 4 ] therefore, most cases are diagnosed at an advanced stage. [ 5 , 6 ] Epithelial ovarian carcinoma has considerable complexity and heterogeneity in biology, drug response, and survival time, representing a major obstacle for its precision medicine.…”

Section: Introductionmentioning

confidence: 99%

Prognostic signature of ovarian cancer based on 14 tumor microenvironment-related genes

Nie

Song

Li³

et al. 2021

Medicine

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Background: Ovarian cancer is one of the lethal gynecological diseases in women. However, using tumor microenvironment related genes to identify prognostic signature of ovarian cancer has not been discussed in detail. Methods: The mRNA profiles of 386 ovarian cancer patients were retrieved from The Cancer Genome Atlas. Univariate Cox regression and LASSO Cox regression analyses were performed and 14 optimized prognostic genes related to tumor microenvironment were identified. Results: The multivariate Cox hazards regression showed risk score was an independent prognostic signature for ovarian cancer. Nomogram model could reliably predict the patients’ survival. Furthermore, M1 macrophages, M2 macrophages, and follicular helper T cells, differentially expressed between the high- and low-risk groups, were found to be associated with the risk score. Conclusion: CTL-associated antigen 4 (CTLA4) and indoleamine 2,3-Dioxygenase 1 (IDO1), which were previously shown to be important immune checkpoints, probably contribute to the immunosuppressive microenvironment aberration. This study may shed light on the prognosis of ovarian cancer.

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IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling

Cited by 6 publications

References 44 publications

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin

Enhanced antitumor efficacy of cisplatin for treating ovarian cancer in vitro and in vivo via transferrin binding

Prognostic signature of ovarian cancer based on 14 tumor microenvironment-related genes

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