Role of p53β in the inhibition of proliferation of gastric cancer cells expressing wild-type or mutated p53

Ji, Wansheng; Ma, Jingrong; Zhang, Hongmei; Zhong, Hua; Li, Lei; Ding, Na; Jiao, Jianxin; Gao, Zhixing

doi:10.3892/mmr.2015.3370

Cited by 13 publications

(9 citation statements)

References 26 publications

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“…Moreover, MDM2 has been shown to influence chromatin modifications by interacting directly with chromatin (61)(62)(63). A p53 mutation was reported in SGC-7901 cells, but its oncostatic function was not blocked completely (64). However, this infers that other components may be involved in the melatonin-induced inhibition of GC cell growth.…”

Section: Discussionmentioning

confidence: 98%

Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

Song

Luo

et al. 2018

Oncol Rep

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Globally, gastric cancer (GC) is one of the most common types of cancer and the third leading cause of cancer‑related death. In China, gastric and liver cancers have the highest mortality rates. Melatonin, also known as N-acetyl‑5-methoxytryptamine, is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness. Melatonin has been shown to inhibit various carcinomas, including GC. There are many different hypotheses to explain the anticancer effects of melatonin, including stimulation of apoptosis, inhibition of cell growth, regulation of anticancer immunity, induction of free-radical scavenging, and the competitive inhibition of estrogen. However, the underlying mechanism by which these effects are elicited remains elusive. The aim of the present study was to investigate the effects of melatonin on human GC cells and determine the underlying molecular mechanism. We treated SGC-7901 GC cells with melatonin and analyzed the resulting protein changes using protein chip technology. Several proteins related to cell apoptosis and proliferation were identified and further tested in SGC-7901 GC cells. We found that melatonin induced cell cycle arrest and the downregulation of CDC25A, phospho-CDC25A (at Ser75), p21 (p21Cip1/p21Waf1) and phospho-p21 (at Thr145). Melatonin also induced upregulation of Bax, downregulation of Bcl-xL, an increase in cleaved caspase-9 level and activation of caspase-3, which confirmed the involvement of the mitochondria in melatonin‑induced apoptosis. Upstream regulators of the above proteins, MDM2, phospho-MDM2 (at Ser166) and AKT, phospho-AKT (at Thr308) were all attenuated by melatonin, which led to an increase in p53. The present study demonstrated that the oncostatic effects of melatonin on SGC-7901 GC cells are mediated via the blockade of the AKT/MDM2 intracellular pathway.

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Section: Discussionmentioning

confidence: 98%

Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

Song

Luo

et al. 2018

Oncol Rep

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“…Furthermore, up-regulation of the p53β isoform is induced by cisplatin or fluorouracil[34], while down-regulation of Δ133p53 is induced by recombinant mutant human tumor necrosis factor[35], indicating that Δ133p53 and p53β isoforms are strong targets for further diagnosis and pharmacological research. Combined with inferences reported by other study groups[8,9], we now realize that Δ133p53 is an essential factor involved in gastritis-associated carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells

Zhang¹,

Sang²,

Wang³

et al. 2017

WJG

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AIMTo investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells.METHODSThe growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53β, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01).RESULTSRT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53β mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53β (r = 0.076, P > 0.01).CONCLUSIONΔ133p53 isoform (not p53β) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.

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“…The present study was designed to investigate the role of p53β in two GC cell lines with differing p53 status, that were treated with cisplatin and/or rmhTNF. The MKN45 GC cell line expresses wild-type p53 (29), while the SGC7901 cell line expresses a mutated form of p53 (GAG→GCG in exon six, corresponding to Glu→Ala in codon 204; (30). The growth of MKN45 cells was inhibited by rmhTNF alone, while the growth of SGC7901 cells was unaffected by rmhTNF.…”

Section: Discussionmentioning

confidence: 99%

Effect of p53β on human gastric cancer cells treated with recombinant mutated human TNF and cisplatin

Yuan

Zhang

et al. 2017

Molecular Medicine Reports

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The present study aimed to investigate the role of tumour protein 53 isoform b (p53β) on human gastric cancer (GC) cell lines treated with recombinant mutated human tumour necrosis factor (rmhTNF) and cisplatin. The Cell Counting Kit‑8 assay was used to assess growth in the GC cell lines MKN45 and SGC7901, following treatment with rmhTNF in the presence or absence of cisplatin. Levels of p53β and bcl‑2 apoptosis regulator (bcl‑2) mRNA were assessed using reverse transcription‑polymerase chain reaction. The results demonstrated that growth was significantly inhibited by either cisplatin or rmhTNF treatments alone in MKN45 cells, and combination treatment with cisplatin and rmhTNF had a synergistic effect on growth inhibition of MKN45 cells. Notably, these observations were not evident in SGC7901 cells, where a mutant form of p53 is present. Treatment of MKN45 cells with rmhTNF did not affect bcl‑2 or p53β mRNA expression levels. However, treatment of MKN45 cells with cisplatin induced upregulation of p53β and downregulation of bcl-2 mRNA expression levels, and these effects were enhanced by combination treatment with rmhTNF. Pearson correlation analysis revealed a negative correlation between the expression of p53β and bcl‑2 mRNA, and a negative correlation between bcl-2 mRNA expression and the inhibition of cell growth. In conclusion, the inhibitory effect of cisplatin on the growth of MKN45 GC cells was enhanced by rmhTNF via unknown mechanisms that involved p53β, indicating that p53β may be an appropriate therapeutic target for the treatment of GC.

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Role of p53β in the inhibition of proliferation of gastric cancer cells expressing wild-type or mutated p53

Cited by 13 publications

References 26 publications

Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells

Effect of p53β on human gastric cancer cells treated with recombinant mutated human TNF and cisplatin

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