Abstract
BackgroundCervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy.MethodsWestern blot was applied to determine the expression of FEN1‐ and apoptosis‐related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo.ResultsOur data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo.ConclusionFEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.
Highlights
Cervical cancer is 1 of the top 10 commonly diagnosed and lethal cancers in female worldwide.[1,2] Radiotherapy has been used as a primary treatment for cervical cancer for many years, especially for locally advanced cervical cancer.[3,4] Ionizing radiation (IR) can affect DNA structure stability and repair processes by directly interacting with any of the individual DNA moieties, or by indirect interaction with the induced reactive species from molecules surrounding DNA
We showed that flap endonuclease‐1 (FEN1) inhibitor enhances ionizing radiation (IR) sensitivity of cervical cancer both in vitro and in vivo, and the beneficial effect was largely due to the impairment of DNA damage repair mechanism resulting from FEN1 inhibition, leading to apoptosis of cancer cells
We determined whether FEN1 inhibitor SC13 could enhance the sensitivity of IR treatment in cervical cancer cells
Summary
Cervical cancer is 1 of the top 10 commonly diagnosed and lethal cancers in female worldwide.[1,2] Radiotherapy has been used as a primary treatment for cervical cancer for many years, especially for locally advanced cervical cancer.[3,4] Ionizing radiation (IR) can affect DNA structure stability and repair processes by directly interacting with any of the individual DNA moieties, or by indirect interaction with the induced reactive species from molecules surrounding DNA. DNA flap endonuclease‐1 (FEN1) is a member of RAD2 superfamily nucleases It plays an essential role in Okazaki fragment maturation of DNA replication, and is an important component in DNA repair pathways such as base excision repair (BER) and polymerase α error editing (AEE) pathway.[19,20,21,22] FEN1 is reported to be overexpressed in many forms of cancer, and FEN1 inhibitor has been reported to enhance the effect of DNA damage‐related chemotherapy drugs such as cisplatin, 5‐FU, and paclitaxel.[18,23,24,25]. We showed that FEN1 inhibitor enhances IR sensitivity of cervical cancer both in vitro and in vivo, and the beneficial effect was largely due to the impairment of DNA damage repair mechanism resulting from FEN1 inhibition, leading to apoptosis of cancer cells
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