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Abnormal activation of notch 1 signaling causes apoptosis resistance in cervical cancer

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E-CENTURY PUBLISHING CORP

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Apoptosis; cell proliferation; cervical cancer; chemoresistance; Notch1 signaling

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The Notch1 signaling pathway is upregulated in cervical cancer and its depletion leads to apoptotic cell death and increased sensitivity to DNA-targeting drugs, suggesting its essential role in cervical cancer progression and apoptosis resistance.
Notch1 signaling pathway is an evolutionarily conserved and crucial regulator to determine cell fate and differentiation. Notch1 is often over expressed in several cancers, which plays an essential for cancer cell proliferation, survival, invasion and metastasis. The oncogenic function of Notch1 signaling in cervical cancer progression is not well-characterized. In the present study, we showed that Notch1 is significantly enhanced in cervical cancer tissues. Similarly, the relative mRNA and expression of Notch1 protein are significantly upregulated in cervical cancer cell lines such as HeLa and SiHa. Further, we have performed RNAi for NOTCH1 depletion to determine its specific role in cervical cancer progression. Flow cytometry analysis revealed that NOTCH1 depletion leads to activation of apoptotic cell death in cervical cancer. Further, the NOTCH1 depleted cells showed increased sensitivity towards DNA-targeting drugs and therefore cell viability was reduced efficiently. Altogether, our findings suggest that Notch1 overexpression in cervical cancer cells was involved in tumorigenesis and apoptosis resistance of cervical cancer.

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