Role of Autophagy in Regulating the Radiosensitivity of Tumor Cells

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2017 Aug 9

PMID 28786037

Citations 18

Authors

Yong Xin

Fan Jiang

Chunsheng Yang

Qiuyue Yan

Wenwen Guo

Qian Huang

Longzhen Zhang

Guan Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Autophagy is a metabolic response of cells to chemical and physical factors, such as nutrition or growth factor deprivation, proinflammatory state, hypoxia, accumulation of reactive oxygen species, presence of infectious agents, and DNA damage. Autophagy maintains the homeostasis of intracellular metabolism mainly by degrading cellular organelles and critical proteins. In a sense, autophagy protects cells from death. Radiotherapy is a powerful tool used to control tumor growth, and it can induce autophagy. The relationship between radiotherapy and autophagy is worthy of further investigation.

Methods: We searched various electronic databases including PubMed for peer-reviewed English-language articles and selected articles on the mechanism of autophagy, its role in cancer development and cancer treatment, and the relationship between the effect of radiation therapy and autophagy intensity.

Results: This review has recently shown that the sensitivity of tumor cells to radiation therapy can be increased by regulating autophagy.

Conclusion: The effects of autophagy vary, and autophagy provides various ways of enhancing radiosensitivity, including inhibition of autophagy, increase in autophagy, and altering the outcome of autophagy.

Citing Articles

Myriad factors and pathways influencing tumor radiotherapy resistance.

Mi L, Zhang H Open Life Sci. 2024; 19(1):20220992.

PMID: 39655194 PMC: 11627069. DOI: 10.1515/biol-2022-0992.

Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies.

Wang P, Chen B, Zhan Y, Wang L, Luo J, Xu J Pharmaceutics. 2022; 14(11).

PMID: 36365098 PMC: 9695556. DOI: 10.3390/pharmaceutics14112279.

CircRNAs in Tumor Radioresistance.

Gao Y, Gao J, Lin F, Wang T, Huo S, Wu J Biomolecules. 2022; 12(11).

PMID: 36358938 PMC: 9687855. DOI: 10.3390/biom12111586.

Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

Zhu L, Zhao Y, Yu L, He X, Wang Y, Jiang P Bioengineered. 2021; 12(1):5516-5528.

PMID: 34528498 PMC: 8806855. DOI: 10.1080/21655979.2021.1965694.

Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.

Kabakov A, Yakimova A Cancers (Basel). 2021; 13(5).

PMID: 33806538 PMC: 7961562. DOI: 10.3390/cancers13051102.

References

Schaaf M, Jutten B, Keulers T, Savelkouls K, Peeters H, van den Beucken T . Canonical autophagy does not contribute to cellular radioresistance. Radiother Oncol. 2015; 114(3):406-12. DOI: 10.1016/j.radonc.2015.02.019. View

Wang Y, Yin W, Zhu X . Blocked autophagy enhances radiosensitivity of nasopharyngeal carcinoma cell line CNE-2 in vitro. Acta Otolaryngol. 2013; 134(1):105-10. DOI: 10.3109/00016489.2013.844365. View

Karagounis I, Kalamida D, Mitrakas A, Pouliliou S, Liousia M, Giatromanolaki A . Repression of the autophagic response sensitises lung cancer cells to radiation and chemotherapy. Br J Cancer. 2016; 115(3):312-21. PMC: 4973160. DOI: 10.1038/bjc.2016.202. View

Moretti L, Yang E, Kim K, Lu B . Autophagy signaling in cancer and its potential as novel target to improve anticancer therapy. Drug Resist Updat. 2007; 10(4-5):135-43. DOI: 10.1016/j.drup.2007.05.001. View

Liang D, El-Zein R, Dave B . Autophagy Inhibition to Increase Radiosensitization in Breast Cancer. J Nucl Med Radiat Ther. 2015; 6(5). PMC: 4657142. DOI: 10.4172/2155-9619.1000254. View

Yao K, Komata T, Kondo Y, Kanzawa T, Kondo S, Germano I . Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. J Neurosurg. 2003; 98(2):378-84. DOI: 10.3171/jns.2003.98.2.0378. View

Bristol M, Emery S, Maycotte P, Thorburn A, Chakradeo S, Gewirtz D . Autophagy inhibition for chemosensitization and radiosensitization in cancer: do the preclinical data support this therapeutic strategy?. J Pharmacol Exp Ther. 2013; 344(3):544-52. PMC: 3583507. DOI: 10.1124/jpet.112.199802. View

Su Y, Yu C, Hsu F, Fu S, Hwang J, Hung L . Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway. Int J Mol Med. 2014; 34(5):1417-22. DOI: 10.3892/ijmm.2014.1927. View

Emery S, Alotaibi M, Tao Q, Selley D, Lichtman A, Gewirtz D . Combined antiproliferative effects of the aminoalkylindole WIN55,212-2 and radiation in breast cancer cells. J Pharmacol Exp Ther. 2013; 348(2):293-302. PMC: 4859093. DOI: 10.1124/jpet.113.205120. View

10.

Ondrej M, Cechakova L, durisova K, Pejchal J, Tichy A . To live or let die: Unclear task of autophagy in the radiosensitization battle. Radiother Oncol. 2016; 119(2):265-75. DOI: 10.1016/j.radonc.2016.02.028. View

11.

Palumbo S, Comincini S . Autophagy and ionizing radiation in tumors: the "survive or not survive" dilemma. J Cell Physiol. 2012; 228(1):1-8. DOI: 10.1002/jcp.24118. View

12.

Zhang X, Shi H, Lin S, Ba M, Cui S . MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncol Rep. 2015; 34(3):1557-64. DOI: 10.3892/or.2015.4078. View

13.

Zarzynska J . The importance of autophagy regulation in breast cancer development and treatment. Biomed Res Int. 2014; 2014:710345. PMC: 4182068. DOI: 10.1155/2014/710345. View

14.

Benbrook D, Long A . Integration of autophagy, proteasomal degradation, unfolded protein response and apoptosis. Exp Oncol. 2012; 34(3):286-97. View

15.

Wilson E, Bristol M, Di X, Maltese W, Koterba K, Beckman M . A switch between cytoprotective and cytotoxic autophagy in the radiosensitization of breast tumor cells by chloroquine and vitamin D. Horm Cancer. 2011; 2(5):272-85. PMC: 3277402. DOI: 10.1007/s12672-011-0081-7. View

16.

Hoyer-Hansen M, Jaattela M . Autophagy: an emerging target for cancer therapy. Autophagy. 2008; 4(5):574-80. DOI: 10.4161/auto.5921. View

17.

He G, Wang Y, Pang X, Zhang B . Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation. Tumour Biol. 2013; 35(2):1003-11. DOI: 10.1007/s13277-013-1134-z. View

18.

Chiu H, Fang W, Chen Y, Wu M, Yuan G, Ho S . Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagy. PLoS One. 2012; 7(7):e40462. PMC: 3389026. DOI: 10.1371/journal.pone.0040462. View

19.

Gravina G, Marampon F, Sherris D, Vittorini F, Di Cesare E, Tombolini V . Torc1/Torc2 inhibitor, Palomid 529, enhances radiation response modulating CRM1-mediated survivin function and delaying DNA repair in prostate cancer models. Prostate. 2014; 74(8):852-68. DOI: 10.1002/pros.22804. View

20.

Wang P, Zhang L, Chen Z, Meng Z . MicroRNA targets autophagy in pancreatic cancer cells during cancer therapy. Autophagy. 2013; 9(12):2171-2. DOI: 10.4161/auto.26463. View