Effect of Lymph Node-Targeted Chemotherapy with Carbon Nanoparticles Absorbing 5-Fluorouracil on Expressions of bcl-2, bax and Caspase-3 in Gastric Cancer Tissues and Metastatic Lymph Nodes_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Bin , LI Ang , ZHANG Bo , CHENG Zhong , CHEN Zhixin , CHEN Jiaping

*Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaCorresponding Author： CHEN Zhi-xin, E-mail： chenzhixin@medmail.com.cn;

Corresponding author：

Keywords：

Gastric cancer; Carbon nanoparticles; bcl-2; bax; Caspase-3【Foundation item】 Science and Technology Supporting Plan of Sichuan Province (No.20085Ｚ0168)

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Objective To determine whether lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU affects expressions of bcl-2, bax and caspase-3 in gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa. Methods Twenty-eight patients with gastric cancer in our department were divided into lymph node-targeted chemotherapy (LNTC) group and control group from October 2005 to August 2006. The patients were treated with carbon nanoparticles absorbing 5-FU before operation in LNTC group and those were operated directly in control group. The gastric cancer tissues, metastatic lymph nodes and normal gastric mucosa were collected after operation. The expressions of bcl-2, bax and caspase-3 in those tissues were determined by immunohistochemical technique. Results In LNTC group, the positive expression rate of bcl-2 in gastric cancer tissues and metastatic lymph nodes was significantly lower than those in control group (28.6% vs . 78.6% , 25.0% vs . 70.0% , P ＜ 0.05), the positive expression rate of bax (85.7% vs . 28.6% , 80.0% vs . 30.0% ) and caspase-3 (57.1% vs . 14.3% , 55.0% vs . 15.0% ) in gastric cancer tissues and metastatic lymph nodes was significantly higher than those in control group ( P ＜ 0.05). The positive expression rate of bcl-2, bax and caspase-3 in normal gastric mucosa was not significantly different between two groups ( P ＞ 0.05). Conclusion The lymph node-targeted chemotherapy with carbon nanoparticles absorbing 5-FU can down-regulate the expression of bcl-2 and up-regulate the expression of bax and caspase-3 in gastric cancer tissues and metastatic lymph nodes, and therefore by affecting the expression levels of these apoptosis molecules may be one of the ways to induce tumor cell apoptosis.

Citation： HUANG Bin,LI Ang,ZHANG Bo,CHENG Zhong,CHEN Zhixin,CHEN Jiaping. Effect of Lymph Node-Targeted Chemotherapy with Carbon Nanoparticles Absorbing 5-Fluorouracil on Expressions of bcl-2, bax and Caspase-3 in Gastric Cancer Tissues and Metastatic Lymph Nodes. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(1): 18-22. doi: Copy

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11.	黄广建，陈忠清，张延龄，等. 胃癌病灶周围注射超微活性炭对淋巴结的显色效果 [Ｊ] . 中华医学杂志， 2004； 84(24)： 2070.
12.	于永扬，王存，郑阳春，等. 比较研究纳米炭示踪剂在低位直肠癌淋巴结清扫及病理检查中的价值 [Ｊ] . 中国普外基础与临床杂志， 2008； 15(5)： 358.
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15.	Kobayashi O, Motohashi H, Sairenji M, et al . Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon clinical study of 5-FU concentration in resected lymph nodes [Ｊ] . Gan To Kagaku Ryoho, 1988; 15(4 Pt 1)： 619.
16.	Huang Y, Hagiwara A, Wang W, et al . Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer [Ｊ] . AntiCancer Drugs, 2002; 13(4)： 431.
17.	梁寒，王仆，王晓娜，等. 活性碳吸附丝裂霉素C腹腔化疗预防进展期胃癌术后复发 [Ｊ] . 中华外科杂志， 2003； 41 (4)： 274.
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1. 黄斌，陈志新. 胃癌淋巴靶向化疗的研究进展 [Ｊ] . 中国普外基础与临床杂志， 2006； 13(5)： 617.
2. Leonardo E, Valente G, Cappia S, et al . Immunohistochemical evaluation of P-glycoprotein in human malignancies by monoclonal antibody MC57 [Ｊ] . Int J Cancer, 1994; 57(6)： 841.
3. 李宏，郑建伟，唐滔, 等. Caspase-3在纳米磁药物靶向治疗胆管移植瘤组织中的表达 [Ｊ] . 中国普外基础与临床杂志， 2006； 13(6)： 685.
4. Anagnostopoulos GK, Stefanou D, Arkoumani E, et al . Bax and Bcl-2 protein expression in gastric precancerous lesions: immunohistochemical study [Ｊ] . J Gastroenterol Hepatol, 2005; 20(11)： 1674.
5. 吴丽华，张玲，韩莹. 凋亡相关基因的表达与胃癌的关系 [Ｊ] . 沈阳医学院学报， 2004； 6(3)： 134.
6. 杨其昌，冯一中，张晓娟，等. Caspase-3、 Bcl-2和Bak在胃癌中的表达及意义 [Ｊ] . 江苏医药， 2006； 32(12)： 1105.
7. Sun Y, Chen XY, Liu J, et al . Differential caspase-3 expression in noncancerous, premalignant and cancer tissues of stomach and its clinical implication [Ｊ] . Cancer Detect Prev, 2006; 30(2)： 168.
8. 杨建辉，张一楚. 转染bcl-2反义寡核苷酸增强5-FU诱导胃癌细胞株SGC-7901凋亡 [Ｊ] . 肿瘤， 2002； 22(5)： 387.
9. 王佐佑，肖冰，时永全，等. 转染Bcl-2反义核酸对胃癌细胞药物敏感性的影响 [Ｊ] . 世界华人消化杂志， 1999； 7(9)： 796.
10. Xu ZW, Friess H, BüChler MW, et al . Overexpression of Bax sensitizes human pancreatic cancer cells to apoptosis induced by chemotherapeutic agents [Ｊ] . Cancer Chemother Pharmacol, 2002; 49(6)： 504.
11. 黄广建，陈忠清，张延龄，等. 胃癌病灶周围注射超微活性炭对淋巴结的显色效果 [Ｊ] . 中华医学杂志， 2004； 84(24)： 2070.
12. 于永扬，王存，郑阳春，等. 比较研究纳米炭示踪剂在低位直肠癌淋巴结清扫及病理检查中的价值 [Ｊ] . 中国普外基础与临床杂志， 2008； 15(5)： 358.
13. 董怡民，沓小容，姚崇舜，等. 纳米活性炭对氟尿嘧啶的吸附和缓释作用的实验研究 [Ｊ] . 中国医科大学学报， 2004； 33 (3)： 205.
14. 粱寒，唐贺文，郝希山，等. 活性炭吸附丝裂霉素C腹腔化疗的药代动力学研究 [Ｊ] . 中华肿瘤杂志， 2005； 27(7)： 412.
15. Kobayashi O, Motohashi H, Sairenji M, et al . Preoperative treatment of lymph node metastases of gastric cancer by local injection of 5-FU adsorbed on activated carbon clinical study of 5-FU concentration in resected lymph nodes [Ｊ] . Gan To Kagaku Ryoho, 1988; 15(4 Pt 1)： 619.
16. Huang Y, Hagiwara A, Wang W, et al . Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer [Ｊ] . AntiCancer Drugs, 2002; 13(4)： 431.
17. 梁寒，王仆，王晓娜，等. 活性碳吸附丝裂霉素C腹腔化疗预防进展期胃癌术后复发 [Ｊ] . 中华外科杂志， 2003； 41 (4)： 274.
18. Rosen HR, Jatzko G, Repse S, et al . Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology [Ｊ] . J Clin Oncol, 1998; 16(8)： 2733.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Lymph Node-Targeted Chemotherapy with Carbon Nanoparticles Absorbing 5-Fluorouracil on Expressions of bcl-2, bax and Caspase-3 in Gastric Cancer Tissues and Metastatic Lymph Nodes

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