Embryonic stem cell microenvironment suppresses the malignancy of cutaneous melanoma cells by down‐regulating PI3K/AKT pathway

Wang, Chenjie; Wang, Xiaoran; Liu, Jiahui; Huang, Zheqian; Li, Chaoyang; Liu, Ying; Sang, Xuan; Liu, Yang; Wang, Shoubi; Su, Yangfeng; Liu, Chengxiu; Liu, Yizhi; Wang, Zhichong

doi:10.1002/cam4.2207

Cited by 12 publications

(15 citation statements)

References 50 publications

(64 reference statements)

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“…Western blotting confirmed that the expression of pro-apoptosis genes Bcl-2, p53, Bax and Caspase3 in U118 cells of GE co-culture group was significantly higher than the control group according to Figure 3D,3E. [13][14][15]. We attempted to use ES cells on a mouse leukemia model and we found that ES cells could significantly improve myelography of mice and prolong their survival.…”

Section: Es Microenvironment Inhibits the Proliferative Ability Of U1mentioning

confidence: 86%

“…Researchers have successfully used the embryonic stem cells to simulate the microenvironment of embryos, confirmed their safety and efficacy in the treatment of leukemic mice, [13] and found that embryonic stem cell microenvironment can reverse the degree of malignancy of uveal melanoma and cutaneous melanoma by downregulating PI3K pathway [14,15]. This study aimed to investigate whether embryonic stem cell microenvironment can reverse the degree of malignancy of human glioma.…”

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confidence: 96%

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The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating PI3K/AKT pathway

liu

wang

et al. 2020

Preprint

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PURPOSETo study the effect of the embryonic stem cell (ESc) microenvironment in inhibiting mouse glioma cells and its possible mechanism. METHODSGlioblastoma cell line U118 in the brain, was investigated in this study. There were four experimental groups: U118 glioma cells cultured alone as the control group (GB group), U118 cell and ESc co-cultured group(GE group), U118 cell and ESc co-cultured and adding phosphoinositide 3-kinase (PI3K) agonist group (GA group), U118 and temozolomide as the positive control group (GT group); U118 cells were harvested after 72 hours of culture. Cell proliferation, apoptosis, reactive oxygen species (ROS) and vasculogenic mimicry assays, quantitative real-time RT-PCR (qPCR), and western blot (WB) were study, the biological function of U118 glioma cells and the PI3K/AKT signaling pathway were compared the differences between the groups. RESULTSCompared with the GB control group, the GE co-culture group and GT chemotherapy group showed reduced cell proliferation, increased apoptosis, increased ROS, decreased or disappearance of vasculogenic mimicry. Expression of cyclin B and D, significantly reduced, while that of BAX, BCL-2, P53, Caspase3, Gsk-3B, P21, and P27, significantly increased. The expression of PI3K, PDK, AKT, and mTOR, significantly decreased while that of PTEN significantly increased. The expression of positive regulatory factors significantly increased but negative regulatory factors decreased in GA group compared to the GE group. CONCLUSIONThe ESC microenvironment reverse glioma malignancy, partially via inhibition of the PI3K signaling pathway. Our study may have a significant impact and clinical implication on cell therapy in glioma.

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Section: Es Microenvironment Inhibits the Proliferative Ability Of U1mentioning

confidence: 86%

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confidence: 96%

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating PI3K/AKT pathway

liu

wang

et al. 2020

Preprint

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“…The ability of the embryonic microenvironment to reverse tumor cells gradually diminishes as the embryo develops and differentiates. Gerschenson et al (21) injected melanoma cells into E10 mouse embryos (12)(13)(14), E14 mouse embryos, and the dorsal skin of newborn mice. The tumor formation rates were 0 (0/5), 73% (32/44), and 80% (16/20), respectively.…”

Section: Discussionmentioning

confidence: 99%

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating the PI3K/AKT pathway

He¹,

Liu²,

Wang³

et al. 2021

Transl Cancer Res TCR

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Background: Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system, accounting for 48.6% of malignant tumors. The current standard treatment plan includes the widest range of safe surgical resection, supplemented by local brain radiotherapy and temozolomide concurrent chemotherapy; this can cause serious side effects. Even so, the median survival time of GBM patients is only 8 months, and the 5-year survival rate is only 5.5%. It is imminent to find new treatments.Early studies have shown that chicken and zebrafish embryos can reprogram cancer cells into a nontumorigenic phenotype through the embryonic microenvironment. However, the effect of embryonic stem cell microenvironment on GBM and its possible mechanism are not clear.Methods: In this study, the glioblastoma cell line, U118, in the brain was investigated. There were four experimental groups: GB, GE, GA and GT. U118 cells were harvested after culturing for 72 hours. Cell proliferation, apoptosis, reactive oxygen species (ROS) were examined using vasculogenic mimicry assays, quantitative real-time polymerase chain reaction (QRT-PCR), western blotting (WB) and flow cytometry.The differences in the biological function of U118 cells and the PI3K/protein kinase B (AKT) signaling pathway were compared between the groups.Results: Compared with the GB control group, the GE co-culture group and GT chemotherapy group showed reduced cell proliferation, increased apoptosis, increased ROS, as well as decreased or inhibited vasculogenic mimicry. Expressions of cyclin B1 and cyclin D1 were also notably reduced, while that of Bax, Bcl-2, p53, Caspase-3, GSK-3β, p21, and p27 were significantly increased. Moreover, the expression of PI3K, AKT, and mTOR were markedly decreased, whereas expression of PTEN increased considerably.Also, the expression of positive regulatory factors significantly increased, however negative regulatory factors decreased in the GA group compared to the GE group. Conclusions:The ESC microenvironment reverses glioma malignancy, partially via inhibition of the PI3K signaling pathway. Our study may have a significant impact and important clinical implications for cell therapy in the treatment of glioma.

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“…Thus, researchers gradually turn their attention to stem cell therapy because of the unmet need for cancer treatment. Since early experiments showed that the zebrafish embryonic environment can reverse the malignant phenotype of cancer (Lee et al, 2005), inspired by this, our laboratory also studied the embryonic stem cell microenvironment (ESC‐ME) and found that ESC‐ME could not only inhibit the malignant behaviors of skin (Wang et al, 2019) and uveal melanoma, but also resist the aging of normal cells and promote their proliferation (Liu et al, 2019). EVs are currently proven to play a key role in the microenvironment of stem cells, thus the effectiveness of SC‐EVs to concurrent reverse aging and anticancer has been preliminarily confirmed.…”

Section: The Relationship Between Evs and Cancer And The Way Sc‐evs Amentioning

confidence: 99%

Therapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer

Liu

Cheng

Wang

et al. 2020

Journal Cellular Physiology

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Senescent cells can secrete a plethora of cytokines which induce senescent phenotype of neighboring cells and was called senescence‐associated secretory phenotype. Previously, it was believed that cancer was caused by the infinite division and uncontrolled proliferation of cells. Based on this, anticancer treatments were all aimed at killing cancer cells. Cancer is now considered an age‐related disease. Cancer cells are not exogenous, but one of the worst results of injuries which initially induce cell senescence. Therefore, reversing cell senescence can fundamentally prevent and treat cancer. Though current anticancer treatments induce the cancer cells apoptosis, they induce senescence of normal cells at the same time, thus promoting the occurrence and development of cancer and forming a vicious circle. Extracellular vesicles (EVs) are nano‐sized vesicles which partially mirror their parent cells. In the tumor microenvironment, EVs of senescent cells can change the expression profile of cancer cells, contributing to their resistance to chemotherapy. There is growing evidence indicates that stem cell EVs exert effective antiaging and anticancer actions by transferring functional microRNAs and proteins. This review will summarize the therapeutic role of stem cell EVs in reversing aging and cancer, which suggests the broad clinical application perspective.

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Embryonic stem cell microenvironment suppresses the malignancy of cutaneous melanoma cells by down‐regulating PI3K/AKT pathway

Cited by 12 publications

References 50 publications

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating PI3K/AKT pathway

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating PI3K/AKT pathway

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating the PI3K/AKT pathway

Therapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer

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