Mechanism of Gemcitabine Resistance in Pancreatic Cancer Chemotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

PAN Bo , GUO Junchao , LIAO Quan , ZHAO Yupei.

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Keywords：

Pancreatic cancer Chemotherapy Gemcitabine Resistance

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【Abstract】Objective To investigate the possible mechanism of gemcitabine resistance in pancreatic cancer chemotherapy.
Methods Recent literatures about the genes and signal pathways those play key roles in mediating gemcitabine chemotherapy resistance of pancreatic cancer were collected and reviewed.
Results Oncogenes like c-Src and bcl-XL, inflammation pathway of NF-κB, cytokines like IL-1β and NO are closely related with the chemoresistance； the relationship between multiple drug resistance relevant genes like MDR1/P-gP and the resistance to gemcitabine remains to be clarified.
Conclusion Genes and pathways like c-Src, bcl-XL, NF-κB, etc. might become new targets to increase the chemotherapeutic sensitivity of pancreatic cancer, however, the mechanism of pancreatic cancer chemotherapy resistance still needs further to be studied.

Citation： PAN Bo,GUO Junchao,LIAO Quan,ZHAO Yupei.. Mechanism of Gemcitabine Resistance in Pancreatic Cancer Chemotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2005, 12(5): 530-532. doi: Copy

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11.	Muerkoster S, Arlt A, Witt M, et al. Usage of the NFkappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer [J]. Int J Cancer, 2003； 104(4)∶469.
12.	Muerkoster S, Wegehenkel K, Arlt A, et al. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin1beta [J]. Cancer Res, 2004； 64(4)∶1331.
13.	Togawa A, Ito H, Kimura F, et al. Establishment of gemcitabineresistant human pancreatic cancer cells and effect of brefeldina on the resistant cell line [J]. Pancreas, 2003； 27(3)∶220.
14.	李驥. 胰腺癌和腫瘤多藥耐藥 [J]. 國外醫學外科學分冊， 2004； 31(2)∶69.
15.	Zhao YP, Zhang LY, Liao Q, et al. Detection of multidrug resistant gene 1 in pancreatic cancer [J]. Hepatobiliary Pancreat Dis Int, 2004； 3(2)∶307.
16.	Miller DW, Fontain M, Kolar C, et al. The expression of multidrug resistanceassociated protein (MRP) in pancreatic adenocarcinoma cell lines [J]. Cancer Lett, 1996； 107(2)∶301.

1. Li D, Xie K, Wolff R, et al. Pancreatic cancer [J]. Lancet， 2004； 363(9414)∶1049.
2. 郭俊超, 趙玉沛. 多藥耐藥基因與胰腺癌化療 [J]. 胰腺病學， 2002； 2(4)∶247.
3. Abrams RA. Adjuvant therapy for pancreatic adenocarcinoma: what have we learned since 1985? [J]. Int J Radiat Oncol Biol Phys, 2003； 56(4 Suppl)∶3.
4. Hochster HS. Newer approaches to gemcitabinebased therapy of pancreatic cancer: fixeddoserate infusion and novel agents [J]. Int J Radiat Oncol Biol Phys, 2003； 56(4 Suppl)∶24.
5. Shi X, Liu S, Kleeff J, et al. Acquired resistance of pancreatic cancer cells towards 5Fluorouracil and gemcitabine is associated with altered expression of apoptosisregulating genes [J]. Oncology， 2002； 62(4)∶354.
6. Duxbury MS, Ito H, Zinner MJ, et al. siRNA directed against cSrc enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity [J]. J Am Coll Surg, 2004； 198(6)∶953.
7. Schniewind B, Christgen M, Kurdow R, et al. Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondriamediated apoptosis [J]. Int J Cancer, 2004； 109(2)∶182.
8. Plath T, Peters M, Detjen K, et al. Overexpression of pRB in human pancreatic carcinoma cells: function in chemotherapyinduced apoptosis [J]. J Natl Cancer Inst, 2002； 94(2)∶129.
9. Fahy BN, Schlieman MG, Virudachalam S, et al. Inhibition of AKT abrogates chemotherapyinduced NFkappaB survival mechanisms: implications for therapy in pancreatic cancer [J]. J Am Coll Surg, 2004； 198(4)∶591.
10. Arlt A, Gehrz A, Muerkoster S, et al. Role of NFkappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabineinduced cell death [J]. Oncogene, 2003； 22(21)∶3243.
11. Muerkoster S, Arlt A, Witt M, et al. Usage of the NFkappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer [J]. Int J Cancer, 2003； 104(4)∶469.
12. Muerkoster S, Wegehenkel K, Arlt A, et al. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin1beta [J]. Cancer Res, 2004； 64(4)∶1331.
13. Togawa A, Ito H, Kimura F, et al. Establishment of gemcitabineresistant human pancreatic cancer cells and effect of brefeldina on the resistant cell line [J]. Pancreas, 2003； 27(3)∶220.
14. 李驥. 胰腺癌和腫瘤多藥耐藥 [J]. 國外醫學外科學分冊， 2004； 31(2)∶69.
15. Zhao YP, Zhang LY, Liao Q, et al. Detection of multidrug resistant gene 1 in pancreatic cancer [J]. Hepatobiliary Pancreat Dis Int, 2004； 3(2)∶307.
16. Miller DW, Fontain M, Kolar C, et al. The expression of multidrug resistanceassociated protein (MRP) in pancreatic adenocarcinoma cell lines [J]. Cancer Lett, 1996； 107(2)∶301.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Mechanism of Gemcitabine Resistance in Pancreatic Cancer Chemotherapy

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