Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2009

Open Access 01-12-2009 | Research

Fractionated irradiation induced radio-resistant esophageal cancer EC109 cells seem to be more sensitive to chemotherapeutic drugs

Authors: Li Xie, Xianrang Song, Jinming Yu, Ling Wei, Bao Song, Xingwu Wang, Liyan Lv

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2009

Login to get access

Abstract

Background

Chemo-radiotherapy, a combination of chemotherapy and radiotherapy, is the most frequent treatment for patients with esophageal cancer. In the process of radiotherapy, the radiosensitive cancer will become a radio-resistant one.

Methods

In order to detect the chemotherapeutic drug sensitivity in radio-resistant cancer cells and improve the therapy efficiency, we firstly established a radio-resistant esophageal cancer cell model (referred to as EC109/R) from the human esophageal squamous cell carcinoma cell line EC109 through fractionated irradiation using X-rays. The radio-sensitivity of EC109/R cells was measured by clonogenic assay. To detect the drug sensitivity for EC109/R compared to its parent cells, we employed MTT method to screen the effectiveness of five different drugs commonly used in clinical therapy. The ratio of apoptosis was examined by flow cytometry.

Results

EC109/R cells were more sensitive to 5-fluorouracil, doxorubicin, paclitaxel and etoposide, but tolerant to cisplatin compared to its original cells.

Conclusion

Our study implies that fractionated irradiation induced radio-resistant esophageal cancer cell is more sensitive to certain kind of chemotherapeutic drugs. It provides evidence for choosing the sequence of radiotherapy and chemotherapy in esophageal cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Law S, Wong J: The current management of esophageal cancer. Adv Surg. 2007, 41: 93-119. 10.1016/j.yasu.2007.05.007.CrossRef Law S, Wong J: The current management of esophageal cancer. Adv Surg. 2007, 41: 93-119. 10.1016/j.yasu.2007.05.007.CrossRef
2.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.CrossRef Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.CrossRef
3.
go back to reference Seitz JF, Dahan L, Jacob J, Artru P, Maingon P, Bedenne L, Triboulet JP: Esophagus cancer. Gastroenterol Clin Biol. 2006, 30 (Spec No 2): 2S5-2S15. Seitz JF, Dahan L, Jacob J, Artru P, Maingon P, Bedenne L, Triboulet JP: Esophagus cancer. Gastroenterol Clin Biol. 2006, 30 (Spec No 2): 2S5-2S15.
4.
go back to reference Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med. 2003, 349 (23): 2241-2252. 10.1056/NEJMra035010.CrossRef Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med. 2003, 349 (23): 2241-2252. 10.1056/NEJMra035010.CrossRef
5.
go back to reference Wright CD: Esophageal cancer surgery in 2005. Minerva Chir. 2005, 60 (6): 431-444. Wright CD: Esophageal cancer surgery in 2005. Minerva Chir. 2005, 60 (6): 431-444.
6.
go back to reference Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, Gu XZ, Zhang DC, Zhang RG, Wang LJ: Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003, 75 (2): 331-336. 10.1016/S0003-4975(02)04401-6.CrossRef Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, Gu XZ, Zhang DC, Zhang RG, Wang LJ: Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003, 75 (2): 331-336. 10.1016/S0003-4975(02)04401-6.CrossRef
7.
go back to reference Ku GY, Ilson DH: Esophageal cancer: adjuvant therapy. Cancer J. 2007, 13 (3): 162-167. 10.1097/PPO.0b013e318074dbe7.CrossRef Ku GY, Ilson DH: Esophageal cancer: adjuvant therapy. Cancer J. 2007, 13 (3): 162-167. 10.1097/PPO.0b013e318074dbe7.CrossRef
8.
go back to reference Brenner B, Ilson DH, Minsky BD: Treatment of localized esophageal cancer. Semin Oncol. 2004, 31 (4): 554-565. 10.1053/j.seminoncol.2004.04.015.CrossRef Brenner B, Ilson DH, Minsky BD: Treatment of localized esophageal cancer. Semin Oncol. 2004, 31 (4): 554-565. 10.1053/j.seminoncol.2004.04.015.CrossRef
9.
go back to reference Ku GY, Ilson DH: Preoperative therapy in esophageal cancer. Clin Adv Hematol Oncol. 2008, 6 (5): 371-379. Ku GY, Ilson DH: Preoperative therapy in esophageal cancer. Clin Adv Hematol Oncol. 2008, 6 (5): 371-379.
10.
go back to reference Liao Z, Cox JD, Komaki R: Radiochemotherapy of esophageal cancer. J Thorac Oncol. 2007, 2 (6): 553-568. 10.1097/01.JTO.0000275339.62831.5e.CrossRef Liao Z, Cox JD, Komaki R: Radiochemotherapy of esophageal cancer. J Thorac Oncol. 2007, 2 (6): 553-568. 10.1097/01.JTO.0000275339.62831.5e.CrossRef
11.
go back to reference Ng T, Dipetrillo T, Purviance J, Safran H: Multimodality treatment of esophageal cancer: a review of the current status and future directions. Curr Oncol Rep. 2006, 8 (3): 174-182. 10.1007/s11912-006-0017-5.CrossRef Ng T, Dipetrillo T, Purviance J, Safran H: Multimodality treatment of esophageal cancer: a review of the current status and future directions. Curr Oncol Rep. 2006, 8 (3): 174-182. 10.1007/s11912-006-0017-5.CrossRef
12.
go back to reference Carcaterrra M, Osti MF, De Sanctis V, Caruso C, Berardi F, Enrici RM: Adjuvant radiotherapy and radiochemotherapy in the management of esophageal cancer: a review of the literature. Rays. 2005, 30 (4): 319-322. Carcaterrra M, Osti MF, De Sanctis V, Caruso C, Berardi F, Enrici RM: Adjuvant radiotherapy and radiochemotherapy in the management of esophageal cancer: a review of the literature. Rays. 2005, 30 (4): 319-322.
13.
go back to reference Bottke D, Koychev D, Busse A, Heufelder K, Wiegel T, Thiel E, Hinkelbein W, Keilholz U: Fractionated irradiation can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines. Radiat Res. 2008, 170 (1): 41-48. 10.1667/RR0986.1.CrossRef Bottke D, Koychev D, Busse A, Heufelder K, Wiegel T, Thiel E, Hinkelbein W, Keilholz U: Fractionated irradiation can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines. Radiat Res. 2008, 170 (1): 41-48. 10.1667/RR0986.1.CrossRef
14.
go back to reference Shimokuni T, Tanimoto K, Hiyama K, Otani K, Ohtaki M, Hihara J, Yoshida K, Noguchi T, Kawahara K, Natsugoe S, et al: Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data. Int J Oncol. 2006, 28 (5): 1153-1162. Shimokuni T, Tanimoto K, Hiyama K, Otani K, Ohtaki M, Hihara J, Yoshida K, Noguchi T, Kawahara K, Natsugoe S, et al: Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data. Int J Oncol. 2006, 28 (5): 1153-1162.
15.
go back to reference Song X, Liu X, Chi W, Liu Y, Wei L, Wang X, Yu J: Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol. 2006, 58 (6): 776-784. 10.1007/s00280-006-0224-7.CrossRef Song X, Liu X, Chi W, Liu Y, Wei L, Wang X, Yu J: Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol. 2006, 58 (6): 776-784. 10.1007/s00280-006-0224-7.CrossRef
16.
go back to reference Suit H: The Gray Lecture 2001: coming technical advances in radiation oncology. Int J Radiat Oncol Biol Phys. 2002, 53 (4): 798-809.CrossRef Suit H: The Gray Lecture 2001: coming technical advances in radiation oncology. Int J Radiat Oncol Biol Phys. 2002, 53 (4): 798-809.CrossRef
17.
go back to reference Ogawa K, Utsunomiya T, Mimori K, Tanaka F, Haraguchi N, Inoue H, Murayama S, Mori M: Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation. Int J Oncol. 2006, 28 (3): 705-713. Ogawa K, Utsunomiya T, Mimori K, Tanaka F, Haraguchi N, Inoue H, Murayama S, Mori M: Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation. Int J Oncol. 2006, 28 (3): 705-713.
18.
go back to reference Gupta S, Ahmed MM: A global perspective of radiation-induced signal transduction pathways in cancer therapeutics. Indian J Exp Biol. 2004, 42 (12): 1153-1176. Gupta S, Ahmed MM: A global perspective of radiation-induced signal transduction pathways in cancer therapeutics. Indian J Exp Biol. 2004, 42 (12): 1153-1176.
19.
go back to reference Ahmed KM, Dong S, Fan M, Li JJ: Nuclear factor-kappaB p65 inhibits mitogen-activated protein kinase signaling pathway in radioresistant breast cancer cells. Mol Cancer Res. 2006, 4 (12): 945-955. 10.1158/1541-7786.MCR-06-0291.CrossRef Ahmed KM, Dong S, Fan M, Li JJ: Nuclear factor-kappaB p65 inhibits mitogen-activated protein kinase signaling pathway in radioresistant breast cancer cells. Mol Cancer Res. 2006, 4 (12): 945-955. 10.1158/1541-7786.MCR-06-0291.CrossRef
20.
go back to reference Ryu JS, Um JH, Kang CD, Bae JH, Kim DU, Lee YJ, Kim DW, Chung BS, Kim SH: Fractionated irradiation leads to restoration of drug sensitivity in MDR cells that correlates with down-regulation of P-gp and DNA-dependent protein kinase activity. Radiat Res. 2004, 162 (5): 527-535. 10.1667/RR3260.CrossRef Ryu JS, Um JH, Kang CD, Bae JH, Kim DU, Lee YJ, Kim DW, Chung BS, Kim SH: Fractionated irradiation leads to restoration of drug sensitivity in MDR cells that correlates with down-regulation of P-gp and DNA-dependent protein kinase activity. Radiat Res. 2004, 162 (5): 527-535. 10.1667/RR3260.CrossRef
21.
go back to reference Hill BT, Moran E, Etievant C, Perrin D, Masterson A, Larkin A, Whelan RD: Low-dose twice-daily fractionated X-irradiation of ovarian tumor cells in vitro generates drug-resistant cells overexpressing two multidrug resistance-associated proteins, P-glycoprotein and MRP1. Anticancer Drugs. 2000, 11 (3): 193-200. 10.1097/00001813-200003000-00007.CrossRef Hill BT, Moran E, Etievant C, Perrin D, Masterson A, Larkin A, Whelan RD: Low-dose twice-daily fractionated X-irradiation of ovarian tumor cells in vitro generates drug-resistant cells overexpressing two multidrug resistance-associated proteins, P-glycoprotein and MRP1. Anticancer Drugs. 2000, 11 (3): 193-200. 10.1097/00001813-200003000-00007.CrossRef
22.
go back to reference Nielsen D, Maare C, Eriksen J, Litman T, Skovsgaard T: Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation. Int J Radiat Oncol Biol Phys. 2001, 51 (4): 1050-1057.CrossRef Nielsen D, Maare C, Eriksen J, Litman T, Skovsgaard T: Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation. Int J Radiat Oncol Biol Phys. 2001, 51 (4): 1050-1057.CrossRef
23.
go back to reference Martin LP, Hamilton TC, Schilder RJ: Platinum resistance: the role of DNA repair pathways. Clin Cancer Res. 2008, 14 (5): 1291-1295. 10.1158/1078-0432.CCR-07-2238.CrossRef Martin LP, Hamilton TC, Schilder RJ: Platinum resistance: the role of DNA repair pathways. Clin Cancer Res. 2008, 14 (5): 1291-1295. 10.1158/1078-0432.CCR-07-2238.CrossRef
24.
go back to reference Borst P, Rottenberg S, Jonkers J: How do real tumors become resistant to cisplatin?. Cell Cycle. 2008, 7 (10): 1353-1359.CrossRef Borst P, Rottenberg S, Jonkers J: How do real tumors become resistant to cisplatin?. Cell Cycle. 2008, 7 (10): 1353-1359.CrossRef
25.
go back to reference Watanabe Y, Koi M, Hemmi H, Hoshai H, Noda K: A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer. Br J Cancer. 2001, 85 (7): 1064-1069. 10.1038/sj.bjc.6692037.CrossRef Watanabe Y, Koi M, Hemmi H, Hoshai H, Noda K: A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer. Br J Cancer. 2001, 85 (7): 1064-1069. 10.1038/sj.bjc.6692037.CrossRef
26.
go back to reference Lin X, Howell SB: DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther. 2006, 5 (5): 1239-1247. 10.1158/1535-7163.MCT-05-0491.CrossRef Lin X, Howell SB: DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther. 2006, 5 (5): 1239-1247. 10.1158/1535-7163.MCT-05-0491.CrossRef
Metadata
Title
Fractionated irradiation induced radio-resistant esophageal cancer EC109 cells seem to be more sensitive to chemotherapeutic drugs
Authors
Li Xie
Xianrang Song
Jinming Yu
Ling Wei
Bao Song
Xingwu Wang
Liyan Lv
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2009
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-28-68

Other articles of this Issue 1/2009

Journal of Experimental & Clinical Cancer Research 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine