Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

Liu, Zhen; Duan, Zhijun; Chang, Jiuyang; Zhang, Zhi Feng; Chu, Rui; Li, Yuling; Dai, Ke-Hang; Mo, Guangquan; Chang, Qingyong

doi:10.1371/journal.pone.0098560

Cited by 34 publications

(32 citation statements)

References 37 publications

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“…Li et al reported that sinomenine induces breast cancer cell death via MAPK signal pathway and reactive oxygen species (ROS) generation (15). Combined chemotherapy with senomenine treatment (25)(26)(27)(28) has been revealed to sensitize multidrug-resistant cancer cells in various cancers. Song et al demonstrated that sinomenine inhibited invasion and migration in breast cancer by suppressing NF-κB activation (17).…”

Section: Discussionmentioning

confidence: 99%

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

Xie

Ren

Lin

et al. 2016

International Journal of Oncology

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Abstract. Osteosarcoma is the most common primary malignant tumor of the bone. The long-term survivals continue to be unsatisfactory for patients with metastatic and recurrent disease. Metastasis is still a severe challenge in osteosarcoma treatment. Sinomenine, an alkaloid from traditional Chinese medicine, has been proved to possess potent antitumor and anti-invasion effect on various cancers. However, the effect of sinomenine on human osteosarcoma and the underlying mechanisms remains unknown. We report here that sinomenine inhibited proliferation by inducing S phase arrest and suppressing the clone formation. Significant inhibitory effects were found in invasion and metastasis in osteosarcoma, but little cytotoxicity was observed in tested concentrations. Exposure to sinomenine resulted in suppression of invasion and migration in osteosarcoma cells as well as tube formation ability in the human umbilical vein endothelial cells (HUVEC) and U 2 OS cells. Furthermore, it demonstrated that CXCR4 played a key role contributing to invasion in osteosarcoma which is considered to be a core target site in sinomenine treatment. Sinomenine inhibited invasion by suppressing CXCR4 and STAT3 phosphorylation then downregulating the expression of MMP-2, MMP-9, RANKL, VEGF downstream. In addition, then RANKL-mediated bone destruction stimulated by osteoclastogenesis and VEGF-related neovascularization were restrained. Importantly, in vivo, sinomenine suppressed proliferation, osteoclastogenesis and bone destruction. Through these various comprehensive means, sinomenine inhibits metastasis in osteosarcoma. Taken together, our results revealed that sinomenine caused S phase arrest, inhibited invasion and metastasis via suppressing the CXCR4-STAT3 pathway and then osteoclastogenesis-mediated bone destruction and neovascularization in osteosarcoma. Sinomenine is therefore a promising adjuvant agent for metastasis control in osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

Xie

Ren

Lin

et al. 2016

International Journal of Oncology

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“…Previous studies have revealed that celecoxib may prevent chemotherapy drug resistance in digestive and gynecologic carcinomas (9)(10)(11)(12), but whether it serves a similar role in T-cell lymphoma has not been determined. The present study demonstrated that celecoxib sensitized Jurkat and Hut-78 cells to various chemotherapy drugs by triggering apoptosis and inhibiting the expression of MDR-associated proteins.…”

Section: Discussionmentioning

confidence: 99%

“…P65, the primary functioning subunit of activated NF-κB, is an important indicator for predicting MDR in tumors, as it promotes cell viability, causes apoptosis resistance and enhances expression of various MDR-associated proteins including P-gp and MRP1 (7). Furthermore, previous studies have also confirmed that the expression of Bcl-2 may be directly upregulated by activation of the NF-κB signaling pathway, thereby inhibiting Bax expression and leading to an anti-apoptotic effect in tumor cells (8)(9)(10)(11). In the present study, the results suggested that the expression of P65, Bcl2, P-gp and MRP1 was significantly decreased, while the expression of Bax was increased in celecoxib-treated Jurkat and Hut-78 cells t compared with those that were not treated with celecoxib.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib enhances sensitivity to chemotherapy drugs of T‑cell lymphoma

Yang

Zhao

et al. 2018

Oncol Lett

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Abstract. Celecoxib is a newly-identified nonsteroidal anti-inflammatory drug, which has been used to treat fever in clinical practice. Celecoxib has been demonstrated to suppress the viability of various human tumor cells. However, the effect of celecoxib on response of T-cell lymphoma to chemotherapy agents remains unclear. The aim of the present study was to investigate the effect of celecoxib on chemosensitivity of human T-cell lymphoma, and to address the underlying mechanism of action. The cytotoxicity of CDDP, epirubicin and VCR on Jurkat and Hut-78 cells treated with celecoxib was assessed by MTT assay, and the half-maximal inhibitory concentration (IC 50 ) value was calculated by Origin 75 software. The effect of celecoxib on apoptosis and intracellular concentration of Rhodamine-123 in Jurkat and Hut-78 cells was analyzed by flow cytometry. The expression of transcription factor p65 (p65), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) at mRNA and protein levels were detected by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Proliferation suppression rates and apoptosis levels were significantly increased in Jurkat and Hut-78 cells combined with celecoxib compared with those without celecoxib, when treated with CDDP, epirubicin and VCR. The IC 50 values of the chemotherapy agents were lower in Jurkat and Hut-78 cells treated with celecoxib compared with those that were not.The apoptosis level, expression of Bax and the intracellular concentration of Rhodamine-123 were increased, whereas the expression of p65, Bcl-2, MDR1 and MRP1 were decreased, in celecoxib-treated Jurkat and Hut-78 cells compared with those without celecoxib treatment. These results indicated that celecoxib may enhance the sensitivity of T-cell lymphoma to chemotherapy drugs by inhibiting the expression of multidrug resistance (MDR)-associated proteins via downregulating the activity of the nuclear factor-κB signaling pathway, suggesting that celecoxib may improve the curative effect of chemotherapy drugs in T-cell lymphoma.

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“…[1][2] Studies have showed that, inhibition of multidrug resistance (MDR) ability of resistant cancer cells would be a good way to achieve successful cancer therapy and to decrease the dose of anticancer drugs. [3][4] In order to reduce the clinical-used drug dosage and side-effects, drug-delivery systems (DDS) have been developed to overcome this problem,because they offered excellent efficient drug transportation.…”

Section: Introductionmentioning

confidence: 99%

Functionalized Multiwalled Carbon Nanotubes as Carriers of Ruthenium Complexes to Antagonize Cancer Multidrug Resistance and Radioresistance

Wang

Feng

Zeng

et al. 2015

ACS Appl. Mater. Interfaces

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Multidrug resistance and radioresistance are major obstacles for successful cancer therapy. Due to the unique characteristics of high surface area, improved cellular uptake, and the possibility to be easily bound with therapeutics, carbon nanotubes (CNTs) have attracted increasing attention as potential nanodrug delivery systems. In this study, a CNT-based radiosensitive nanodrug delivery system was rationally designed to antagonize the multidrug resistance in hepatocellular carcinoma. The nanosystem was loaded with a potent anticancer ruthenium polypyridyl complex (RuPOP) via π-π interaction and formation of a hydrogen bond. The functionalized nanosystem (RuPOP@MWCNTs) enhanced the cellular uptake of RuPOP in liver cancer cells, especially drug-resistant R-HepG2 cells, through endocytosis. Consistently, the selective cellular uptake endowed the nanosystem amplified anticancer efficacy against R-HepG2 cells but not in normal cells. Interestingly, RuPOP@MWCNTs significantly enhanced the anticancer efficacy of clinically used X-ray against R-HepG2 cells through induction of apoptosis and G0/G1 cell cycle arrest, with the involvement of ROS overproduction, which activated several downstream signaling pathways, including DNA damage-mediated p53 phosphorylation, activation of p38, and inactivation of AKT and ERK. Moreover, the nanosystem also effectively reduces the toxic side effects of loaded drugs and prolongs the blood circulation in vivo. Taken together, the results demonstrate the rational design of functionalized carbon nanotubes and their application as effective nanomedicine to overcome cancer multidrug resistance.

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Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

Cited by 34 publications

References 37 publications

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway

Celecoxib enhances sensitivity to chemotherapy drugs of T‑cell lymphoma

Functionalized Multiwalled Carbon Nanotubes as Carriers of Ruthenium Complexes to Antagonize Cancer Multidrug Resistance and Radioresistance

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