RGD-modified oncolytic adenovirus-harboring shPKM2 exhibits a potent cytotoxic effect in pancreatic cancer via autophagy inhibition and apoptosis promotion

Xu, Yanan; Chu, Liang; Yuan, Sujing; Yang, Yong; Ye, Yu; Xu, Bin; Zhang, Kangjian; Liu, Xinyuan; Wang, Ruwei; Fang, Ling; Chen, Zhi‐Nan; Liang, Zongsuo

doi:10.1038/cddis.2017.230

Cited by 22 publications

(13 citation statements)

References 55 publications

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“…Apoptosis is the classic mechanism by which chemotherapy agents induce cell death; 11 however, numerous studies have shown that these drugs also induce autophagy. 12 Autophagy is usually considered to be a critical process by which cells recycle ineffectual cellular components to maintain homeostasis. This process plays a critical role in programmed cell death type II, which can be exploited to suppress tumour growth.…”

mentioning

confidence: 99%

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Zhu

Liu

et al. 2017

Cell Death Dis

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Osteosarcoma is one of the most malignant neoplasms in adolescents, and it generally develops multidrug resistance. Escin, a natural mixture of triterpene saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated potent anti-tumour potential in vitro and in vivo. In the present study, we found that escin inhibited osteosarcoma proliferation in a dose- and time-dependent manner. Additionally, escin-induced apoptosis was evidenced by the increased expression of caspase-related proteins and the formation of apoptotic bodies. Escin also induced autophagy, with elevated LC3, ATG5, ATG12 and Beclin expression as well as autophagosome formation. Inhibition of escin-induced autophagy promoted apoptosis. Moreover, p38 mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK inhibitor partially attenuated the autophagy and apoptosis triggered by escin, but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling pathway; these findings provide evidence for escin as a novel and potent therapeutic for the treatment of osteosarcoma.

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confidence: 99%

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Zhu

Liu

et al. 2017

Cell Death Dis

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“…The results revealed that autophagy activator rapamycin reversed the inhibiting effect on cell proliferation caused by PKM2 knockdown, while autophagy inhibitor 3-MA rescued the inducement of cell proliferation caused by PKM2 overexpression. Pioneer studies demonstrated that PKM2 knockdown caused impairment of the autophagic process, and consequently inhibited pancreatic cancer cell growth 41 . Based on the aforementioned results, we further investigate whether Beclin-1 is involved in PKM2-mediated autophagic cell survival.…”

Section: Discussionmentioning

confidence: 99%

Glycolytic Enzyme PKM2 Mediates Autophagic Activation to Promote Cell Survival in NPM1-Mutated Leukemia

Wang¹,

Yang²,

Yang³

et al. 2019

Int. J. Biol. Sci.

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Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been defined as a distinct leukemia entity in the 2016 updated WHO classification of myeloid neoplasm. Our previous report showed that autophagic activity was elevated in NPM1-mutated AML, but the underlying molecular mechanisms remain elusive. Mount of study provides evidence that glycometabolic enzymes are implicated in the autophagic process. Pyruvate kinase isoenzyme M2 (PKM2), a key glycolytic enzyme, has been recently reported as a tumor supporter in leukemia. However, little is known about the roles of PKM2 in autophagic activity in NPM1-mutated AML. In this study, PKM2 highly expressed in NPM1-mutated AML, and partially, high levels of PKM2 were upregulated by PTBP1. Further experiments demonstrated that PKM2 mediated autophagic activation and increased the phosphorylation of key autophagy protein Beclin-1. Importantly, functional experiments demonstrated that PKM2 contributed to cell survival via autophagic activation. Ultimately, high PKM2 expression was associated with short overall and event-free survival time in NPM1-mutated AML patients. Our findings indicate for the first time that glycolytic enzyme PKM2 mediates autophagic activation and further contributes to cell survival in NPM1-mutated AML, suggesting that PKM2 may serve as a promising target for treatment of NPM1-mutated AML.

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“…The tumor volume of the six mice in each group was measured every three days and estimated using the following equation: (length × width2)/2 [12,13]. At the end of the experiment, mice were killed and the tumors were resected for H&E staining and immunofluorescence staining analyses [14, 15, 16].…”

Section: Methodsmentioning

confidence: 99%

Prostate Cancer-Specific of DD3-driven oncolytic virus-harboring mK5 gene

Hao

Xie

et al. 2018

Open Medicine

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AbstractProstate cancer (PCa) is the second most diagnosed cancer in Western male population. In this study, we insert mK5 (the mutational kringle5 of human plasminogen) into a DD3-promoted (differential display code 3) oncolytic adenovirus to construct OncoAd.mK5.DD3. E1A.dE1B, briefly, OAd.DD3.mK5. DD3 is one of the most prostate cancer specific promoters which can transcriptionally control adenoviral replication. mK5 has been proved to be able to inhibit the tumor angiogenesis and inhibit cell proliferation. Our results suggested that targeting PCa with OAd.DD3.mK5 elicited strong antitumor effect.

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RGD-modified oncolytic adenovirus-harboring shPKM2 exhibits a potent cytotoxic effect in pancreatic cancer via autophagy inhibition and apoptosis promotion

Cited by 22 publications

References 55 publications

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Glycolytic Enzyme PKM2 Mediates Autophagic Activation to Promote Cell Survival in NPM1-Mutated Leukemia

Prostate Cancer-Specific of DD3-driven oncolytic virus-harboring mK5 gene

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