HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells

Cai, Yongsong; Xu, Peng; Liu, Yang; Xu, Ke; Zhu, Jia‐Lin; Wu, Xiaoqing; Jiang, Congshan; Yuan, Qiling; Wang, Bo; Li, Yuanbo; Qiu, Yusheng

doi:10.1038/srep37845

Cited by 17 publications

(10 citation statements)

References 52 publications

(67 reference statements)

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“…Under normal conditions, autophagy protects cells against pro-apoptotic factors ( 45 , 46 ). However, autophagy can also play a role similar to apoptosis, leading to autophagic cell death in some cases.…”

Section: Discussionmentioning

confidence: 99%

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

Zhu

Cai

et al. 2018

Oncol Rep

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Beclin1 is an important autophagy-related protein, which is involved in both autophagy and apoptosis. In recent years, the antitumor effect of Beclin1 has received increased attention. In the present study, we established a stable Beclin1-overexpressing cell line with SW982 human synovial sarcoma cells. We found that Beclin1 overexpression decreased the cell viability, inhibited proliferation and induced apoptosis in SW982 cells. The expression levels of Bcl-2 and PCNA were decreased, while the levels of cleaved-caspase-3 and cleaved-PARP were increased. Beclin1 is closely related with autophagy, thus the autophagy-related markers LC3 and p62 were detected by western blot analysis, and transmission electron microscopy was used to observe autophagosomes. The results showed that the expression level of LC3II was increased and that of p62 was decreased. Moreover, many double membrane-enclosed autophagosomes were found in cells with Beclin1 overexpression, which indicated that the autophagic activity was enhanced. To explore the effect of autophagy on the viability of SW982 cells, Atg5 was knocked down using siRNA to inhibit the autophagic activity. We found that autophagy contributed to the decrease in cell viability. Knockdown of Atg5 increased the viability and decreased the apoptotic rate of SW982 cells with Beclin1 overexpression. The expression level of Bcl-2 was increased, while the expression levels of cleaved-caspase-3 and cleaved-PARP were decreased. We also found that the Akt/Bcl-2/caspase-9 pathway was involved. The phosphorylation of AKT was positively correlated with cell viability. The cleavage of caspase-9 was increased by Beclin1 overexpression and decreased by inhibition of autophagy. Altogether, our results suggested that both autophagy and apoptosis contributed to the antitumor effect of Beclin1 in SW982 cells.

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Section: Discussionmentioning

confidence: 99%

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

Zhu

Cai

et al. 2018

Oncol Rep

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“…Autophagy is a survival strategy employed by cells experiencing nutrient deprivation or other stresses, which is a tightly regulated by the lysosomal degradation pathway, and is considered to be essential for cell growth, differentiation, development, survival and homeostasis. However, while autophagy is generally considered to be a survival mechanism under normal homeostatic conditions, it has both pro-death and pro-survival roles in cancer (21,23). Chemotherapeutic drugs can induce both apoptosis and autophagy in the treatment of cancer, and it was previously reported that autophagy helps cancer cells evade apoptosis, and thus contributes to chemoresistance (24).…”

Section: Discussionmentioning

confidence: 99%

“…Previous research demonstrated the cytoprotective role of autophagy in response to 5-FU treatment in gastric cancer cells (27,28), while a different study showed that 5-FU may suppress miR-30 to upregulate beclin-1 and thus induce autophagic cell death and cell proliferation arrest in gastric cancer cells (29). Nevertheless, many studies have shown that autophagy protects various tumor cells against apoptosis induced by chemotherapeutic drugs (23,30,31).…”

Section: Discussionmentioning

confidence: 99%

miR‑30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy

Liu

Luan

et al. 2017

Exp Ther Med

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Abstract.Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP-resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by exposing the cells to gradually increasing drug concentrations, and miR-30a expression was detected by reverse transcription-semi quantitative polymerase chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC-7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into the cells, and a Cell Counting Kit-8 assay was performed to analyze the chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis were also used to measure MDR1 mRNA and P-glycoprotein expression, and the light chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the chemotherapeutic CDDP in the different groups was assessed using flow cytometry. The results demonstrated that low expression of miR-30a was associated with chemoresistance in gastric cancer cells, and in the chemoresistant cell line SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells). These results suggested that autophagy may contribute to drug resistance in gastric cancer cells, and that the reduction of LC3-II in response to miR-30a overexpression may inhibit chemoresistance-associated autophagy in gastric cancer cells.

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“…Besides, some studies indicated that oxymatrine may prevent pulmonary hypertension through its anti-proliferative, anti-inflammatory, and antioxidant effects 10 . Oxymatrine can induce apoptotic cell death of human pancreatic cancer 11 and prostate cancer 12 Some research found that oxymatrine combining HMGB1 may be more effective in the treatment of human synovial sarcoma and oxymatrine may induce autophagy 13 . These studies suggested that matrine and oxymatrine may be effective in anti-tumor activities.…”

Section: Introductionmentioning

confidence: 99%

Anti-Cervical Cancer Role of Matrine, Oxymatrine and Sophora Flavescens Alkaloid Gels and its Mechanism

Zhou¹,

Guo²,

Yang³

et al. 2018

J. Cancer

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Background: Cervical cancer is one of the leading severe malignancies throughout the world. Sophra flavescens alkaloid (SFA) gels, a compound Traditional Chinese Medicine, has been clinically used in China for many years. Its individual active ingredients are matrine and oxymatrine, which has been showed that they can restrain primary tumorigenesis, while the underlying molecular mechanisms of SFA gels in cervical cancer cells remain unclear.Methods: To detect the effect of SFA gels and its active ingredients, CCK-8 assay and colony assay were used on cervical cancer cells proliferation. Transwell assay was used to detect cancer cell migration. Apoptosis and cell cycle arrest were used to detect whether SFA gels effect the cervical cancer cells proliferation. Western blot was used to detect whether SFA gels regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway.Results: SFA gels can restrain cervical cancer cell proliferation, inhibit metastasis, induce cell cycle arrest in G2/M phase, induce cellular apoptosis through stimulation of Bax and E-cadherin, and suppression of Bcl-2, cyclin A, MMP2. Further study shows that SFA gels may regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway.Conclusions: SFA gels, like its active ingredients, can restrain cervical cancer cells proliferation, suppress cervical cancer cell migration, induce the apoptosis and cell cycle arrest in cervical cancer cells. SFA gels may be a potential anti-tumor therapeutic agent for treating cervical cancer.

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HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells

Cited by 17 publications

References 52 publications

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

miR‑30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy

Anti-Cervical Cancer Role of Matrine, Oxymatrine and Sophora Flavescens Alkaloid Gels and its Mechanism

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