ABSTRACT
Background: Although pancreatic cancer is typically radio-sensitive, local treatment failure and metastasis are commonly caused by the development of resistance to radiotherapy. In the current study, the radio-sensitizing actions of zoledronic acid (ZOL) on pancreatic cancer cells were investigated. Materials and methods: Three human pancreatic cancer cell lines were exposed to ZOL, ionizing radiation (IR), or a combination of both, and the effects of the respective drug regimens on cell proliferation and invasion were examined. Results: Combined treatment with low doses of ZOL plus IR efficiently increased cell death and attenuated cell invasion compared with the individual use of ZOL or IR. These effects of ZOL were associated with inactivation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB). Conclusion: Collectively, these data suggest that ZOL in combination with IR is a promising therapeutic strategy for enhancing radio-sensitivity in pancreatic cancer cells via downregulation of the STAT3/NF-κB signaling pathway.
ABSTRACT
BACKGROUND: The ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer. MATERIALS AND METHODS: The mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan-Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes. RESULTS: We found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor. CONCLUSION: Dysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer.
ABSTRACT
The tumor suppressor characteristics of cyclindependent kinase 10 (CDK10) in nasopharyngeal carcinoma and breast cancer have been previously demonstrated. In the present study the expression status of CDK10 and its prognostic significance in gastric cancer was determined, as well as its role in cell proliferation and invasion. Immunoblot analysis revealed that CDK10 protein expression was notably decreased in gastric cancer compared with normal tissues. Immunohistochemistry demonstrated that the loss of CDK10 expression, which was observed in 50.8% of primary gastric cancer tissues (n=128), significantly correlated with advanced tumor stage (P<0.001), frequent lymph node metastasis (P<0.001), distant metastasis (P=0.013), tumor differentiation (P=0.004) and unfavorable overall survival (P<0.001). Multivariate analysis suggested that CDK10 expression may serve as an independent prognostic predictor (P=0.001) for the progression of gastric cancer. In addition, ectopic CDK10 expression inhibited gastric cancer cell proliferation, migration and invasion, while knockdown of CDK10 promoted these phenotypes. Collectively, the results of the present study indicated that CDK10 expression may serve as a novel prognostic biomarker that holds therapeutic promise for gastric cancer.
