具核梭杆菌对结直肠癌小鼠化疗敏感性的影响

Effect of Fusobacterium nucleatum on chemotherapy sensitivity in mice with colorectal cancer

目的研究具核梭杆菌对结直肠癌小鼠化疗敏感性的影响。方法建立结直肠癌荷瘤小鼠,分为空白对照组、5-氟尿嘧啶对照组和实验组、奥沙利铂实验组和对照组、伊立替康实验组和对照组、阿霉素实验组和对照组、丝裂霉素实验组和对照组,每组5只;各实验组荷瘤鼠灌胃给予具核梭杆菌菌液(10~9CFU),0.2 mL/d,1次/周。连续灌胃4周后,5-氟尿嘧啶实验组、阿霉素实验组、丝裂霉素实验组荷瘤鼠分别腹腔注射给予30.00 mg/(kg·d)、1.75 mg/(kg·d)、2.00 mg/(kg·d)对应药物,1次/d,连用7 d;奥沙利铂实验组、伊立替康实验组荷瘤鼠分别第1天腹腔注射给予29 mg/kg、66 mg/kg对应药物,其余6 d用生理盐水0.1 mL代替。各对照组荷瘤鼠除不灌胃具核梭杆菌菌液外,其余操作均与实验组相同。对比各实验组和对照组的瘤重和抑瘤率(IR%)。结果各组成瘤裸鼠一般情况均正常,肿瘤呈膨胀性生长,未见明显浸润或转移发生。各实验组荷瘤鼠的瘤重(g)均显著大于对照组荷瘤鼠[(1.42±0.15)vs(0.97±0.12),(1.76±0.16)vs(1.45±0.13),(1.50±0.09)vs(1.03±0.08),(1.38±0.07)vs(0.87±0.05),(1.26±0.08)vs(0.79±0.05);均P<0.05],IR%显著小于对照组荷瘤鼠[(27.55±2.83)vs(50.51±5.02),(10.20±1.78)vs(26.02±2.36),(23.47±2.76)vs(47.45±4.86),(29.59±3.02)vs(55.61±5.35),(35.71±3.47)vs(59.69±5.45);均P<0.05]。结论具核梭杆菌降低抗结直肠癌药物的敏感性。

Objective To study the effect of Fusobacterium nucleatum on chemosensitivity of colorectal cancer mice. Methods Colorectal cancer-bearing mice were established and divided into blank control group, 5-fluorouracil control group and observation group, oxaliplatin observation group and control group, irinotecan observation group and control group, doxorubicin observation group and control group, mitomycin observation group and control group, respectively, 5 in each group. The observation groups were given intragastric administration of Fusobacterium nucleus(10~9 CFU), 0.2 mL/d, once/week. After consecutive gavage for 4 weeks, the observation groups of 5-fluorouracil, doxorubicin and mitomycin were given intraperitoneal injection of 30.00 mg/(kg·d), 1.75 mg/(kg·d) and 2.00 mg/(kg·d) of corresponding drugs respectively, once a day for 7 days;while the observation groups of oxaliplatin and irinotecan were given intraperitoneal injection of 29 mg/kg and 66 mg/kg of corresponding drugs respectively on the first day, and 0.1 mL of normal saline for the remaining 6 days. All the control groups were given the same treatment as their corresponding observation groups except the gavage of Fusobacterium nucleus. The tumor weight and tumor inhibition rate(IR%) in each observation group and control group were compared. Results The tumors of all the nude mice were normal, showing swelling and no obvious infiltration or metastasis. The tumor weight(g) in each observation group was significantly higher than that in the corresponding control group [(1.42±0.15) vs(0.97±0.12),(1.76±0.16) vs(1.45±0.13),(1.50±0.09) vs(1.03±0.08),(1.38±0.07) vs(0.87±0.05),(1.26±0.08) vs(0.79±0.05);all P<0.05], and the IR% was significantly lower than in the control group [(27.55±2.83) vs(50.51±5.02),(10.20±1.78) vs(26.02±2.36),(23.47±2.76) vs(47.45±4.86),(29.59±3.02) vs(55.61±5.35),(35.71±3.47) vs(59.69±5.45), all P<0.05]. Conclusion Fusobacterium nucleatum reduces the sensitivity to anti-colorectal cancer drugs.