Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

Wang, Jingquan; Wu, Zhuo‐Xun; Yang, Yuqi; Li, Jin-Sui; Yang, Dong‐Hua; Fan, Ying-Fang; Chen, Zhe‐Sheng

doi:10.3389/fonc.2021.731260

Cited by 6 publications

(10 citation statements)

References 48 publications

(64 reference statements)

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“…Despite the link between MRP-7 expression and chemoresistance, earlier investigations have also suggested that MRP-7 may play other biological roles during carcinogenesis and cancer progression (9)(10)(11)(12)36). MRP-7 expression has been found to be high in lung cancer tissues, while it was rarely detected in normal lung tissues (36).…”

Section: Discussionmentioning

confidence: 99%

“…Other research has recently revealed that MRP-7 stimulates cell proliferation and attenuates apoptosis in human leukemia cells ( 11 ). In ovarian cancer cells, MRP-7 has also been shown to trigger EMT-related signaling and promote cell migration ( 12 ). Our in vitro and in vivo experiments have confirmed that increased MRP-7 expression is a negative prognostic factor in EC patients, and MRP-7 can boost cell proliferation and invasion in EC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of MRP-7 inhibits apoptosis and promotes cell proliferation in human leukemia cells ( 11 ). Interestingly, MRP-7 has been shown to promote ovarian cancer cell motility and cause epithelial-mesenchymal transition (EMT) ( 12 ). It is unclear whether MRP-7 contributes to paclitaxel resistance in EC cells and mediates their invasive abilities.…”

Section: Introductionmentioning

confidence: 99%

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A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7

et al. 2021

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Endometrial cancer (EC) is one of the most frequent gynecological tumors, and chemoresistance is a major obstacle to improving the prognosis of EC patients. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have recently emerged as crucial chemoresistance regulators that alter the levels of downstream target genes. Multidrug Resistance Protein 7 (MRP-7/ABCC10) is an ATP-binding cassette transporter that causes the resistance to anti-cancer drugs. The purpose of this research is to determine whether MRP-7 has a role in mediating the sensitivity of EC cells to paclitaxel and whether the expression of MRP-7 is regulated by miR-98 and lncRNA NEAT1. We reported that the levels of MRP-7 were significantly increased in EC tissues and associated with an unfavorable prognosis. Downregulation of MRP-7 in EC cells sensitized these cells to paclitaxel and reduced cell invasion. PLAUR serves as a downstream molecule of MRP-7 and facilitates paclitaxel resistance and EC cell invasiveness. Moreover, miR-98 serves as a tumor suppressor to inhibit MRP-7 expression, leading to the repression of paclitaxel resistance. Furthermore, a novel lncRNA, NEAT1, was identified as a suppressor of miR-98, and NEAT1 could upregulate MRP-7 levels by reducing the expression of miR-98. Taken together, these findings demonstrate that upregulation of MRP-7 and NEAT1, and downregulation of miR-98 have important roles in conferring paclitaxel resistance to EC cells. The modulation of these molecules may help overcome the chemoresistance against paclitaxel in EC cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7

et al. 2021

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“…Cepharanthine exhibits a variety of potent activities, including inhibition of the NF-κB signaling pathway [ 6 ], activation of the AMPK (adenosine 5′ monophosphate-activated protein kinase) signaling pathway [ 7 ], blockade of autophagosome–lysosome fusion [ 8 ], inhibition of the STAT3 (signal transducer and activator of transcription 3) signaling pathway [ 9 ], scavenging of free radicals and prevention of lipid peroxidation [ 10 ], and binding to heat shock proteins [ 11 ]. Moreover, it also plays a role in processes such as inhibition [ 12 , 13 ] or promotion [ 14 , 15 ] of cell proliferation and cell cycle arrest [ 16 , 17 , 18 , 19 ]. It also exhibits antiviral [ 12 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], antiparasitic [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], antimicrobial [ 36 , 37 , 38 ], bone resorption inhibition [ 39 , 40 , 41 ], antitumor [ 6 , 12 , 13 , 16 , 42 , 43 ], anti-inflammatory [ 7 , 44 , 45 , 46 , …”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity of Cepharanthine

et al. 2023

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Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant Stephania Cephalantha Hayata, is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we aimed to describe the pharmacological properties and mechanisms of cepharanthine, mainly including antitumor, anti-inflammatory, anti-pathogen activities, inhibition of bone resorption, treatment of alopecia, treatment of snake bite, and other activities. At the same time, we analyzed and summarized the potential antiviral mechanism of cepharanthine and concluded that one of the most important anti-viral mechanisms of cepharanthine may be the stability of plasma membrane fluidity. Additionally, we explained its safety and bioavailability, which provides evidence for cepharanthine as a potential drug for the treatment of a variety of diseases. Finally, we further discuss the potential new clinical applications of cepharanthine and provide direction for its future development.

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“…Energy supply, efflux pumps, and ATP-binding cassette (ABC) transporters are all possible MDR mechanisms that permit drug efflux, resulting in a decrease in intracellular drug concentrations and therapeutic medication effectiveness [5][6][7][8]. Mitochondria, recognized as the energy engine of a cell, are emerging as essential drivers of numerous aspects of cancer biology, such as metabolic reprogramming, acquisition of metastatic capacity, and chemotherapeutic response [9].…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin

Chen

et al. 2022

J Exp Clin Cancer Res

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Background Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mitochondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments. Methods A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC. Results The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell proliferation and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3′-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellular DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, promote DOX accumulation, and reverse DOX resistance. Conclusions Our results demonstrated that circ_0000098 is an oncogenic circRNA that promotes HCC development through the miR-383/MCUR1 axis and targeting circ_0000098 with DOX/sh-1@PLT may be a promising and practical therapeutic strategy for preventing DOX resistance in HCC.

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Establishment and Characterization of a Novel Multidrug Resistant Human Ovarian Cancer Cell Line With Heterogenous MRP7 Overexpression

Cited by 6 publications

References 48 publications

A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7

A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7

Pharmacological Activity of Cepharanthine

Hsa_circ_0000098 is a novel therapeutic target that promotes hepatocellular carcinoma development and resistance to doxorubicin

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