p53 is a tumor suppressor gene whose mutation is highly associated with tumorigenesis. The present study investigated the role of p53β in the inhibition of proliferation of gastric cancer cell lines expressing wild-type or mutated p53. Wild-type p53 is expressed in MKN45 cells, but deleted in KATOIII cells, whereas mutated p53 is expressed in SGC7901 cells. The mRNA expression levels of p53β and Δ133p53 were detected in MKN45, SGC-7901 and KATOIII gastric cancer cell lines using nested polymerase chain reaction (PCR). The mRNA expression levels of p53, p53β and B-cell lymphoma 2-associated X protein (Bax) were detected in the MKN45 and SGC-7901 cells following treatment with cisplatin by reverse transcription-PCR. The inhibition of cellular proliferation following treatment with cisplatin was measured by MTT assay. The results of the present study demonstrated that both p53β and Δ133p53 mRNA were expressed in the MKN45 cells, whereas only p53β mRNA was expressed in the SGC7901 cells. No expression of p53β or Δ133p53 mRNA was detected in the KATOIII cells. Following treatment with cisplatin, the number of both MKN45 and SGC-7901 cells was significantly reduced (P<0.001). In the MKN45 cells, p53β, p53 and Bax mRNA expression levels gradually increased with the dose of cisplatin, and the expression of p53β was positively correlated with the expression of p53 (tr=6.358, P<0.05) and Bax (tr=8.023, P<0.05). In the SGC-7901 cells, the expression levels of p53β, p53 and Bax mRNA did not alter with the dose of cisplatin, and the expression of p53β was positively correlated to the expression of p53 (tr=26.41, P<0.01) but not that of Bax. The present study identified the different roles of the p53β isoform in gastric cancer cells with different p53 backgrounds. Enhanced knowledge regarding the p53 status is required for the development of specific biological therapies against gastric cancer.
5‑fluorouracil (5‑FU) is commonly used in the treatment of gastric cancer; however, resistance to this drug occurs under hypoxic conditions. Celecoxib may be used to reverse this resistance. The aim of the present study was to elucidate the inhibitory effects and mechanisms of 5‑FU and celecoxib on the gastric cancer cell line SGC7901 under hypoxic conditions. SGC7901 cells were divided into four groups: Hypoxic control group, 5‑FU group, celecoxib group and 5‑FU/celecoxib combination group. Following treatment, the inhibition rates of cells were determined using an MTT assay. Protein and messenger RNA (mRNA) expression of hypoxia‑inducible factor 2α (HIF‑2α), adenosine triphosphate‑binding cassette sub‑family G member 2 (ABCG2) and octamer binding protein 4 (Oct‑4) were determined using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The results demonstrated that the 5‑FU/celecoxib combination group had a significantly higher inhibition rate than the individually treated 5‑FU and celecoxib groups (P<0.05); inhibition rates were 66.09, 52.61 and 46.1%, respectively. mRNA and protein expression levels of HIF‑2α, ABCG2 and Oct‑4 were significantly lower in the celecoxib and 5‑FU/celecoxib combination groups (P<0.01) compared with those of the hypoxia control and 5‑FU groups. The 5‑FU group demonstrated the highest levels of the respective mRNA and proteins. In conclusion, the results of the present study indicated that celecoxib had anti‑tumor effects, as it was shown to inhibit tumor cell growth via the inhibition of HIF‑2α, ABCG2 and Oct‑4. The 5‑FU/celecoxib combination had a synergic effect on tumor growth inhibition. This therefore suggested that inhibition of HIF‑2α, ABCG2 and Oct‑4 may be a potential method of reducing chemotherapy resistance and enhancing the effectiveness of chemotherapy treatment.
BACKGROUND Gastric glomus tumor (GGT) is rare submucosal mesenchymal tumor that lacks specific clinical manifestations and is usually treated mainly by traditional surgical resection. This paper presents a case of a GGT, exhibited both intraluminally and extraluminally growth that was removed by laparoscopy-gastroscopy cooperative surgery. CASE SUMMARY A 52-year-old male presented with epigastric discomfort accompanied by a sense of fullness for 3 mo. Upper gastrointestinal endoscopy identified a submucosal lump located in the gastric antrum. Endoscopic ultrasonography identified a 2.4 cm × 1.8 cm lump located in the gastric antrum. It originated from the muscularis propria and exhibited both intraluminally and extraluminally growth, with hypoechoicity on the periphery, hyperechoicity in the middle, and unclear boundaries. Computed tomography showed nodular thickening of 3.0 cm × 2.2 cm in the gastric wall of the gastric antrum, and after enhancement, the lesion exhibited obvious enhancement We suspected that it was a gastrointestinal stromal tumor (glomus tumor and schwannoma were not excluded) and planned to perform laparoscopy-gastroscopy cooperative surgery. Immunohistochemical staining after the operation revealed that spinal muscular atrophy (+), h-caldesmon (+), cluster of differentiation 34 (CD34) (+), 2% Ki-67-positive rate, CD56, melanoma antigen, CD117, discovered on GIST-1, leukocyte common antigen, caudal type homeobox 2, cytokeratin, and S-100 were all negative. The tumor was finally diagnosed as a GGT. CONCLUSION GGTs are rare submucosal tumors of the stomach and should be considered in the differential diagnosis of gastric submucosal tumors. Laparoscopy-gastroscopy cooperative surgery is less invasive and more precise and could be an effective method for the treatment of GGTs.
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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