FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis

Abstract

Radioresistance is a main reason for local recurrence of esophageal squamous cell carcinoma (ESCC). Forkhead box M1 (FoxM1) is implicated in cancer progression and chemoresistance. This study aims to determine the role of FoxM1 in ESCC radioresistance. We found that FoxM1 protein was upregulated in ESCC tissues compared with adjacent normal tissues. In vitro assays revealed that following irradiation, Eca-109, TE-13, and KYSE-150 cells had increased levels of FoxM1 protein. FoxM1 knockdown resulted in significantly reduced colony formation and increased cell apoptosis following irradiation. Moreover, FoxM1 knockdown induced ESCC cells to accumulate in the radiosensitive G2 /M phase and impeded the repair of radiation-induced DNA damage. Mechanistic studies indicated that radiosensitization of ESCC enhanced by FoxM1 knockdown was associated with increased BAX/BCL2 ratio as well as downregulated Survivin and XIAP, followed by the activation of both extrinsic and intrinsic apoptosis pathways. In xenograft mouse model, the combination of radiation and FoxM1-shRNA led to a synergistic anti-tumor effect. In conclusion, FoxM1 is a promising target to enhance radiosensitivity of ESCC.

The Large Molecular Weight Polysaccharide from Wild Cordyceps and Its Antitumor Activity on H22 Tumor-Bearing Mice

“…We further discovered massive necrosis and apoptosis of tumor cells after WCP treatment through HE and TUNEL experiments (p < 0.05). Increased tumor cell apoptosis inhibits cell malignancy and slows tumor proliferation [40]. Apoptosis is a complex mechanism involving two main pathways, the endogenous and exogenous pathways.…”

“…We also discovered that WCP significantly up-regulated the expression of Bax and Cyto-c, especially the ratio of Bax/Bcl2. Some studies have shown that the upregulation of Bax/Bcl2 ratio promoted apoptosis in esophageal cancer [40] as well as prostate, bladder, and renal cancer cells [47]. The ratio of the amount of Bax to Bcl-2 protein determines the ratio of homodimer to heterodimer, which plays a key role in susceptibility to apoptosis [48].…”

SPIN1 accelerates tumorigenesis and confers radioresistance of non-small cell lung cancer via orchestrating the FOXO3a/FOXM1 axis

“…Previous studies have shown that FOXM1 is abundantly expressed in NSCLC and various other cancer (18, 19). Moreover, FOXM1 overexpression was involved in cell cycle, apoptosis and DNA repair regulation, thereby facilitating tumorigenesis and chemoradioresistance through different mechanisms (18,(20)(21)(22)(23).…”