Effect of 188Re-IGF-1 analogue in proliferation inhibition and apoptosis induction in pancreatic carcinoma cells / 中华核医学与分子影像杂志

ABSTRACT

Objective To investigate the effect of 188Re-IGF-1 analogue (IGF-1A) in proliferation inhibition and apoptosis induction in human pancreatic carcinoma cell line Patu8988.Methods IGF-1A was labeled with 188Re.Patu8988 cells were divided into an un-treated control group,IGF-1A group (1,5,10,20 μg),188ReO4-group (0.37,1.85,3.70,7.40 MBq) and 188Re-IGF-1A group (0.37,0.74,1.85 MBq).The cell proliferation inhibition effects by the 188Re-IGF-1A and 188ReO4-were detected every day by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test from 1 d to 7 d after administration,while the IGF-1 A group was tested every day from 1 d to 6 d after treatment.Inhibition rates were calculated.At 3 d after treatment with 188ReO4-and 188Re-IGF-1A (1.85,3.70,7.40 MBq),cell apoptosis was detected by flow cytometry.For biodistribution studies of 188Re-IGF-1A,36 nude mice bearing Patu8988 cell xenografts were divided into6 groups.At different time points (15 min,1 h,4 h,1 d,3 d and5 d),36 mice (n =6 per time point) were sacrificed and organs of interest were removed,weighted and measured for radioactivity by a gamma counter.The absorbed doses of organs were calculated as ％ ID/g.One-way analysis of variance was used.Results After 4 d,inhibition rate of Patu8988 cell proliferation in the 188 Re-IGF-1A group (1.85 MBq) was (90.75 ±5.20) ％,higher than that in 188ReO4-group or IGF-1A group ((49.50±2.39)％,(23.00±4.21)％; F=554.724,P＜0.01).At 3 d after treatment with different doses of 188 Re-IGF-1A (1.85,3.70,7.40 MBq),floating cell ratios were (16.56 ± 0.95) ％,(33.39 ±5.93) ％ and (43.76 ± 1.38) ％,respectively.Apoptosisratios in the floating cells treated by 188 Re-IGF-1A (1.85,3.70,7.40 MBq) were (12.70±2.27)％,(17.80±1.51)％ and (23.23 ±1.22)％,respectively.Distribution in tumors was (39.30 ± 17.98),(10.59 ± 9.39),(5.32 ± 1.53) and (5.30 ±2.28) ％ ID/g at the 15 min,1 d,3 d,and 5 d timepoints after intratumoral injection,respectively.The absorbed dose of tumors was 5165.8 mGy/MBq.Conclusions Proliferation of human pancreatic carcinoma cell line Patu8988 can be inhibited and apoptosis can also be induced by 188Re-IGF-1A.The tumor region is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188 Re-IGF-1A.