|Table of Contents|

Targeting Base Excision Repair Pathway to Overcome Doxorubicin Resistance in Colorectal Cancer Cells(PDF)

《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

Issue:
2023年02期
Page:
61-69
Research Field:
生物学
Publishing date:

Info

Title:
Targeting Base Excision Repair Pathway to Overcome Doxorubicin Resistance in Colorectal Cancer Cells
Author(s):
Wang Yuanyuan; Yin Xuechen; Dong Yunfei; Liu Jie; Guo Zhigang; He Lingfeng
(School of Life Sciences,Nanjing Normal University,Jiangsu Key Laboratory for Molecular and Medical Biotechnology,Nanjing 210023,China)
Keywords:
DNA repair;  FEN1;  Doxorubicin;  colorectal cancer cells;  tumor therapy
PACS:
R73-36+1
DOI:
10.3969/j.issn.1001-4616.2023.02.008
Abstract:
Colorectal cancer(CRC)has very high morbidity and mortality, becoming the third most common malignancy and the second most deadly cancer worldwide. As a chemotherapeutic drug, doxorubicin has been widely used in clinical treatment for many years but the therapeutic efficacy is limited due to drug resistance and side effects. Studies have shown that DNA repair capacity is greatly enhanced in cancer cells, which to a large extent enables cancer cells to survive DNA damage induced by chemotherapeutic drugs. Flap endonuclease 1(FEN1)expression gets elevated in various types of cancer cells and plays a critical role in DNA damage repair. The study revealed that FEN1 inhibitor SC13 significantly enhanced the therapeutic effect of doxorubicin. The combinative treatment suppressed colorectal cancer cells proliferation via the activation of cylinD-CDK4-6/INK4/Rb pathway. It suggested that targeting FEN1 could be a potent strategy for tumor-targeting therapy.

References:

[1]SUNG J J Y,LAU J Y,GOH K L,et al. Increasing incidence of colorectal cancer in Asia:implications for screening[J]. Lancet oncology,2005,6(11):871-876.
[2]WANG J,LUO L,WANG D,et al. Combination adjuvant chemotherapy with targeted drugs for treatment of colorectal cancer:A network meta-analysis[J]. Journal of cellular biochemistry,2018,119(2):1521-1537.
[3]KWAK M S,YU S J,YOON J H,et al. Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model[J]. Journal of cancer research and clinical oncology,2015,141(11):2037-2045.
[4]LEI H,WANG X,WU C. Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations[J]. Journal of molecular graphics & modelling,2012,38:279-289.
[5]XUE J P,WANG G,ZHAO Z B,et al. Synergistic cytotoxic effect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells[J]. Oncology reports,2014,32(4):1647-1653.
[6]FORREST R A,SWIFT L P,REPHAELI A,et al. Activation of DNA damage response pathways as a consequence of anthracycline-DNA adduct formation[J]. Biochemical pharmacology,2012,83(12):1602-1612.
[7]MINOTTI G,MENNA P,SALVATORELLI E,et al. Anthracyclines:Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity[J]. Pharmacological reviews,2004,56(2):185-229.
[8]KOZOVSKA Z,GABRISOVA V,KUCEROVA L. Colon cancer:Cancer stem cells markers,drug resistance and treatment[J]. Biomedicine & pharmacotherapy,2014,68(8):911-916.
[9]LUEPERTZ R,WAETJEN W,KAHL R,et al. Dose- and time-dependent effects of doxorubicin on cytotoxicity,cell cycle and apoptotic cell death in human colon cancer cells[J]. Toxicology,2010,271(3):115-121.
[10]QU J,ZHAO L,ZHANG P,et al. MicroRNA-195 chemosensitizes colon cancer cells to the chemotherapeutic drug doxorubicin by targeting the first binding site of BCL2L2 mRNA[J]. Journal of cellular physiology,2015,230(3):535-545.
[11]MOHAJERI M,SAHEBKAR A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance:A review[J]. Critical reviews in oncology hematology,2018,122:30-51.
[12]SHERR C J,BEACH D,SHAPIRO G I. Targeting CDK4 and CDK6:from discovery to therapy[J]. Cancer discovery,2016,6(4):353-367.
[13]CANEPA E T,SCASSA M E,CERUTI J M,et al. INK4 proteins,a family of mammalian CDK inhibitors with novel biological functions[J]. Iubmb life,2007,59(7):419-426.
[14]PANDEY K,AN H J,KIM S K,et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer:A review[J]. International journal of cancer,2019,145(5):1179-1188.
[15]HELLEDAY T,PETERMANN E,LUNDIN C,et al. DNA repair pathways as targets for cancer therapy[J]. Nature reviews cancer,2008,8(3):193-204.
[16]VISNES T,GRUBE M,HANNA B M F,et al. Targeting BER enzymes in cancer therapy[J]. DNA repair,2018,71:118-126.
[17]CLEARY J M,AGUIRRE A J,SHAPIRO G I,et al. Biomarker-guided development of DNA repair inhibitors[J]. Molecular cell,2020,78(6):1070-1085.
[18]ZHENG L,DAI H,ZHOU M,et al. Fen1 mutations result in autoimmunity,chronic inflammation and cancers[J]. Nature medicine,2007,13(7):812-819.
[19]ZHENG L,JIA J,FINGER L D,et al. Functional regulation of FEN1 nuclease and its link to cancer[J]. Nucleic acids research,2011,39(3):781-794.
[20]LAM J S,SELIGSON D B,YU H,et al. Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score[J]. Bju international,2006,98(2):445-451.
[21]NIKOLOVA T,CHRISTMANN M,KAINA B. FEN1 is overexpressed in testis,lung and brain tumors[J]. Anti-cancer research,2009,29(7):2453-2459.
[22]HE L,ZHANG Y,SUN H,et al. Targeting DNA flap endonuclease 1 to impede breast cancer progression[J]. Ebiomedicine,2016,14:32-43.
[23]BROWER V. Modified gastric cancer chemotherapy:more effective,less toxic[J]. Lancet oncology,2015,16(16):E590-E596.
[24]TAHOVER E,PATIL Y P,GABIZON A A. Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index:focus on liposomes[J]. Anti-cancer drugs,2015,26(3):241-258.
[25]ZHANG R,SAITO R,SHIBAHARA I,et al. Temozolomide reverses doxorubicin resistance by inhibiting P-glycoprotein in malignant glioma cells[J]. Journal of neuro-oncology,2016,126(2):235-242.
[26]YANG G,JIANG O,LING D,et al. MicroRNA-522 reverses drug resistance of doxorubicin-induced HT29 colon cancer cell by targeting ABCB5[J]. Molecular medicine reports,2015,12(3):3930-3936.

Memo

Memo:
-
Last Update: 2023-06-15