Combined effects of all-trans-retinoic acid and trichostatin A on the induction of differentiation of thyroid carcinoma cells
- VernacularTitle:维甲酸联合曲古抑素对甲状腺癌细胞的诱导分化作用
- Author:
Yuan GENG-BIAO
1
;
Kuang AN-REN
;
Fan QUN
;
Yu LI-BE
;
Mi YAN-XIA
Author Information
1. 重庆医科大学附属第二医院
- Keywords:
All-trans-retinoic acid(RA);
Trichostain A(TSA);
differentiated thyroid carcinoma(DTC)
- From:Chinese Journal of Cancer
2010;29(4):415-421
- CountryChina
- Language:Chinese
-
Abstract:
Background and Objective: The effectiveness rate of all-trans-retinoic acid(RA)is only about 30% in the clinical application of inducing thyroid carcinoma differentiation.In addition,there are severe toxic side effects,which limit its clinical application.Phase Ⅰ-Ⅲ clinical studies have been conducted on the combined application of two or more kinds of inductors in tumors.Nevertheless,the combination of RA with histone deacetylase inhibitors is rarely reported.This article studied the effects of differentiation for papillary thyroid carcinoma and follicular thyroid carcinoma cell lines induced by RA combined with trichostatin A(TSA),enhancing the effect of induction,while reducing the toxic side effects of a single drug,to provide a theoretical basis for preclinical trials.Methods: After incubation with RA combined with TSA,K1 and FTC-133 were grouped into Group 1(RA 1×10-4 mol/L plus TSA 1.65×10-7 mol/L),Group 2(RA 1×10-4 mol/L plus TSA 3.31×10-7 mol/L),Group 3(RA 1×10-5 mol/L plus TSA 1.65×10-7mol/L),Group 4(RA 1×10-5 mol/L plus TSA 3.31×10-7 mol/L)by four varied concentrations and three time points(12,24,and 48 h).The cell proliferation,conformation,toxic effect,and induced differentiation on K1 and FTC-133 cell lines were studied microscopically with hematoxylin-eosin(HE)to observe cell quantity and morphology,methyl-thiazolyl-tetrazolium(MTT)to calculate cell survival rates,and electrochemiluminescence analysis to measure in vitro thyroglobulin(Tg)levels.Results: The research showed that K1 and FTC-133 cells had cell spacing increases,with an outer edge of smooth,nuclear chromatin condensation after RA combined TSA.Survival rates were assessed by an analysis of variance(ANOVA)by concentration and time point,F values of K1 were 23.52 and 170.14,and F values of FTC-133 were 57.09 and 224.35,respectively.There were significant differences for both cells(P <0.01).The SNK analysis indicated that survival rates were in the order of Group 20.05),yet a significant difference was seen between the other groups.Conclusions: Lower concentrations of RA combined with lower concentrations of TSA have both inhibited cell proliferation,decreased toxicity of the drugs,and increased the effect of K1 and FTC-133 cell differentiation.The mechanism of action may be that TSA has pretranscription DNA regulation and that RA has posttranscriptional signal regulation to enhance the effects ofinhibited proliferation and differentiation of cells by transcription systems.
