Freeman J W, Strodel W E, McGrath P C
University of Kentucky Medical Center, Division of General Surgery, Lexington, Kentucky 40536-0084, USA.
J Gastrointest Surg. 1997 Sep-Oct;1(5):454-60. doi: 10.1016/s1091-255x(97)80133-3.
p120 antisense oligodeoxynucleotides were used to determine whether they inhibited cell growth of MIA PaCa-2, a highly tumorigenic human pancreatic carcinoma cell line. Growth inhibition assays were determined in vitro by the ability of these oligomers to inhibit DNA synthesis and cell growth. For in vivo studies, nude mice were injected with cells and palpable tumors were found in 16 of 20 animals by day 14. Sixteen animals (8 in each group) were then treated daily (25 mg/kg intraperitoneally) for up to 40 days with nonsense control oligomers or p120 antisense oligomers. p120 Antisense oligomers inhibited the in vitro proliferation of MIA PaCa-2 cells in a dose-dependent manner, and optimal growth inhibition of greater than 90% was achieved at an antisense oligomer concentration of 100 micromol/L. The tumor volume was calculated for antisense- and nonsense-treated animals. Fifteen days after the beginning of treatment, control animals had a significantly greater (P=0.0035) tumor volume (425=244 mm3 above baseline) as compared to p120 antisense-treated animals (166+/-116 mm3). Seven of the eight control animals formed tumors that had a volume greater than 1200 mm3 45 days after treatment was begun, whereas only three of eight p120 antisense-treated animals had tumors that were this large. Two of the latter three animals had relatively large, palpable tumors (>150 mm3) prior to treatment. Twenty days after treatment was stopped (day 60), all animals had tumors larger than 1200 mm3. p120 Antisense oligomers were effective for inhibiting in vitro growth of the pancreatic cancer cell line MIA PaCa-2. In preliminary studies, p120 antisense oligomers appeared to inhibit the rate of growth in nude mice; however, no cures were achieved. The most effective response was seen in animals with initial low tumor burden.
使用p120反义寡脱氧核苷酸来确定它们是否抑制MIA PaCa - 2（一种高致瘤性的人胰腺癌细胞系）的细胞生长。通过这些寡聚物抑制DNA合成和细胞生长的能力在体外进行生长抑制测定。对于体内研究，给裸鼠注射细胞，到第14天时，20只动物中有16只可触及肿瘤。然后将16只动物（每组8只）用无义对照寡聚物或p120反义寡聚物每天（腹腔注射25 mg/kg）治疗长达40天。p120反义寡聚物以剂量依赖性方式抑制MIA PaCa - 2细胞的体外增殖，在反义寡聚物浓度为100微摩尔/升时实现了大于90%的最佳生长抑制。计算了反义处理组和无义处理组动物的肿瘤体积。治疗开始15天后，与p120反义处理组动物（166±116立方毫米）相比，对照动物的肿瘤体积（比基线高425±244立方毫米）显著更大（P = 0.0035）。在开始治疗45天后，8只对照动物中有7只形成的肿瘤体积大于1200立方毫米，而8只p120反义处理组动物中只有3只的肿瘤这么大。后三只动物中有两只在治疗前有相对较大的可触及肿瘤（>150立方毫米）。治疗停止20天后（第60天），所有动物的肿瘤都大于1200立方毫米。p120反义寡聚物可有效抑制胰腺癌细胞系MIA PaCa - 2的体外生长。在初步研究中，p120反义寡聚物似乎抑制了裸鼠的生长速度；然而，未实现治愈。在初始肿瘤负荷较低的动物中观察到了最有效的反应。
