2ME2 increase radiation-induced apoptosis of keloid fibroblasts by targeting HIF-1α in vitro.

BACKGROUND: Radiation therapy is considered to be a treatment for keloid scarring; however, radioresistance has been shown to be a serious impediment to treatment efficacy. There is therefore a need for the discovery of novel critical molecular targets whose inhibition might enhance the radiotherapeutic response. An elevated level of hypoxia inducible factor (HIF)-1α expression after radiation therapy in keloid fibroblasts has been demonstrated in our recent experiments. Therefore, we suggested there was a possible close relationship between HIF-1α and keloid radioresistance. The current study aimed to investigate whether target HIF-1α may enhance the radiotherapeutic efficacy of keloids.

METHODS: 2-methoxyestradiol (2ME2) was applied to inhibit HIF-1α expression, and the treatment results were assessed by cell proliferation, apoptosis and radiosensitivity. A lentivirus-mediated small interfering RNA (siRNA) transduction method was used to block the expression of HIF-1α gene.

RESULTS: Both mRNA and protein levels can be effectively inhibited after the knockdown of HIF-1α, leading to a significant increase of radiation-induced apoptosis in keloid fibroblasts. Our experiment also demonstrated that 2ME2 could effectively inhibit the protein expression of HIF-1α, which significantly increased the late stage of radiation-induced apoptosis of keloid fibroblasts.

CONCLUSIONS: The present study indicates that HIF-1α might serve as a therapeutic target for keloids. Furthermore, suppression of HIF-1α by 2ME2 may be a promising therapeutic adjuvant in radiation therapy for keloids.