Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Ying, Huanchun; Qu, Donghui; Liu, Chia‐Chuan; Ying, Tianshu; Lv, Jingwen; Jin, Shanshan; Xu, Huibin

doi:10.3892/ol.2015.2950

Cited by 24 publications

(27 citation statements)

References 32 publications

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“…The antitumor effect of Beclin1 has been confirmed in many previous studies, and Beclin1 gene deletion has been found in ovarian ( 29 – 31 ), breast ( 32 , 33 ), prostate ( 34 , 35 ) and other tumors ( 36 – 39 ). However, the underlying mechanism of this phenomenon remains unclear, which has caused a lot of controversy.…”

Section: Discussionsupporting

confidence: 52%

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: Discussionsupporting

confidence: 52%

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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“…Anti-apoptotic protein BCL-2 overexpression is the most common mechanism of apoptosis evasion, which has been reported be involved in the resistance of cells in a variety of drugs, including doxorubicin, paclitaxel, etoposide, camptothecin, mitoxantrone and cisplatin25, 26, 27. Several other factors, including aberrant activation of protein kinase B, nuclear factor kappa B (NF- κ B), phosphatase and tensin homolog (PTEN) have also been demonstrated to play an important role in developing drug resistance in various cancer types through interfering apoptosis machinery28, 29, 30 (Fig. 1).…”

Section: Mechanisms Of Multidrug Resistancementioning

confidence: 99%

Regulation of multidrug resistance by microRNAs in anti-cancer therapy

An¹,

Sarmiento

Tan

et al. 2017

Acta Pharmaceutica Sinica B

168

132

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Multidrug resistance (MDR) remains a major clinical obstacle to successful cancer treatment. Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression. Accumulating evidence shows that miRNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of miRNAs in regulating MDR in cancer treatment.

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“…Changes in BECN1 and LC3B expression have been reported as features of the cancer state. Some findings suggest that BECN1 is upregulated in glioma and colorectal cancers, leading to poor prognosis in patients [65–67], while others observe a reduction in BECN1 and LC3B expression, leading to the tumor progression in gliomas and other cancer types [34, 68–71]. These differences may underscore the complexity of the role of autophagy in cancer progression as well as differences in tissue type and origin [23, 72].…”

Section: Discussionmentioning

confidence: 99%

Hydrogel Environment Supports Cell Culture Expansion of a Grade IV Astrocytoma

2017

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Malignant astrocytomas are aggressive cancers of glial origin that can develop into invasive brain tumors. The disease has poor prognosis and high recurrence rate. Astrocytoma cell lines of human origin are an important tool in the experimental pathway from bench to bedside because they afford a convenient intermediate system for in vitro analysis of brain cancer pathogenesis and treatment options. We undertook the current study to determine whether hydrogel culture methods could be adapted to support the growth of astrocytoma cell lines, thereby facilitating a system that may be biologically more similar to in vivo tumor tissue. Our experimental protocols enabled maintenance of Grade IV astrocytoma cell lines in conventional monolayer culture and in the extracellular matrix hydrogel, Geltrex™. Light and fluorescence microscopy showed that hydrogel environments promoted cellular reorganization from dispersed cells into multilayered aggregates. Transmission electron microscopy revealed the prevalence of autophagy and nuclear membrane distortions in both culture systems. Analysis of microarray Gene Expression Omnibus (GEO) DataSets highlighted expression of genes implicated in pathways for cancer progression and autophagy. A pilot quantitative polymerase chain reaction (qPCR) analysis of the autophagic biomarkers, Beclin 1 (BECN1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B), with two reference genes (beta actin, ACTB; glyceraldehyde 3-phosphate dehydrogenase, GAPDH), uncovered a relative increase of BECN1 and LC3B in hydrogel cultures of astrocytoma as compared to the monolayer. Taken together, results establish that ultrastructural and molecular characteristics of autophagy are features of this astrocytoma cell line, and that hydrogel culture systems can afford novel opportunities for in vitro studies of glioma.

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Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Cited by 24 publications

References 32 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

Regulation of multidrug resistance by microRNAs in anti-cancer therapy

Hydrogel Environment Supports Cell Culture Expansion of a Grade IV Astrocytoma

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