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Objective: To explore the inhibitory effect of non-functioning pituitary adenoma (NFPA) cells after a combined treatment of adenovirus mediated D2S gene and bromocriptine in vitro., Methods: Adenovirus containing dopamine 2 receptor short isoform (D2S) gene was used to infect NFPA cells. The transfection of D2S gene into NFPA cells was confirmed by immunofluorescence. And cell apoptosis of infected cells treated by bromocriptine was evaluated with CCK-8 assay in vitro., Results: When D2S gene transfection and bromocriptine was used in combination, the survival rate of NFPA cells significantly decreased (40 ± 5)% versus the control group (97 ± 5)% and the pAd-EGFP transfection combined bromocriptine treatment group (90 ± 9)% (P < 0.05)., Conclusion: The combined treatment of adenovirus-mediated D2S gene and bromocriptine can effectively induce the apoptosis of NFPA cells on primary culture and increase the sensitivity of NFPA to dopamine agonist.

Objective: To investigate the change of chemosensitivity of hepatocarcinoma cell line (HepG(2)/ADM) after treated by bromocriptine (BCT) combination with human tumor necrosis factor-alpha (TNF-alpha)., Methods: Firstly, TNF-alpha gene was transfected into HepG(2)/ADM cell line by liposome to establish a cell model expressing the TNF-alpha protein stably. All experiments were divided into four groups and named blank control group (group A), drug resistant group HepG(2)/ADM (group B), TNF-alpha gene group HepG(2)/ADM/TNF (group C) and BCT group (group D) respectively. And group D came from group C treated with BCT simultaneously. MTT assay was tested to detect the sensitivity to ADM of each group and Rhodamine 123 (Rh123) was applied to test the function of P-gp by flow cytometric analysis (FCM). MDR associated genes and proteins and PKC-alpha protein were detected by immunohistochemistry (IHC), Western blot and reverse transcriptase polymerase chain reaction (RT-PCR) methods, respectively. The expression and the apoptosis rate of Bcl-2 in the hepatocarcinoma cells were detected by FCM., Results: There was significant difference between group C and D in the rate of reversing resistance and the intracellular Rho123 accumulation (P < 0.01). MDR1 mRNA and P-gp protein expression in group C and D were low similar to that in group A, but no difference could be found among them (P > 0.05). As we found that PKC-alpha protein expression was downregulated in group D but Bcl-2 protein expression was downregulated in group C, and there was significant difference compared to other groups. The apoptosis rate of hepatocarcinoma cells was much higher in group D than that in group C (P < 0.01) with FCM, but similar to group A (P > 0.05)., Conclusions: Synergistic effect of BCT and TNF-alpha on reversing hepatocellular carcinoma multidrug resistance could enhance the susceptibility of HepG(2)/ADM cells to cytotoxic drugs.

Objective: To investigate the mechanism of reversing multidrug resistance of hepatocarcinoma by bromocriptine (BCT) in vitro and in vivo., Methods: Three groups of cultured HepG2 cells were used: HepG2 (group A), the multidrug resistance HepG2/ADM cells (group B), and the HepG2/ADM cells treated with BCT (group C). Rhodamine 123 test was used to detect the function of P-gp protein. MTT assay was performed to examine the IC50. Multidrug resistance index to common five anticancer drugs of different concentrations of BCT and immunocytochemistry was performed to detect the expression of PKC-a protein. P-gp protein levels of the cells of each group were determined by Western blot. In addition, HepG2 and HepG2/ADM were injected into the livers of the nude mice (NM) (named NM HepG2, NM ADM, NM BCT groups respectively). The BCT group mice were treated with bromocriptine through gastric feedings. The sizes of the tumor growths in the livers were measured using B ultrasound. The MDR1mRNA levels in these tumor tissues were determined by reverse transcription polymerase chain reaction (RT-PCR) and the apoptosis rates of them were measured with TUNEL assay. 99mTc-MIBI SPECT was performed to detect the tumor 99mTc-MIBI accumulation index before and after the BCT treatment., Results: The rate of reversing resistance to ADM by BCT was 45.68% shown by using MTT assay, and the intracellular Rho123 accumulation increased more than two times compared with the control group shown by flow cytometric assay at the concentration of 10 micromol/L BCT and the effect was time-dependent. Between group B and group C there was a significant difference in the expression of PKC-alpha protein by immunocytochemistry detection (q = 5.37, P < 0.01), but there was no significant difference in the expression of P-gp protein between the two groups (q = 1.86, P > 0.05) . There was no notable difference of growth rates of the transplanted liver tumors among the three NM groups (F = 6.39, P > 0.05), and the inhibition rate of tumor volume and weight in NM BCT was higher than that in NM ADM (q1 = 5.89, q2 = 4.92, P < 0.01), but similar to that in NM HepG2 (q1 = 2.47, q2 = 3.02, P > 0.05). No difference was detected in MDR1mRNA between NM ADM and NM BCT using RT-PCR (q = 3.71, P > 0.05). The average number of apoptotic cells per high-power field (25.7+/-1.8) in NM BCT tumor tissues was higher than that in group ADM (2.7+/-0.2) (q = 3.72, P < 0.01), but similar to that of NM HepG2 (23.9+/-1.6) (q = 1.43, P > 0.05). The uptake of 99mTc-MIBI in all the NM after BCT therapy was significantly higher than that before the BCT treatment (t = 3.58, P < 0.01)., Conclusions: BCT can reverse multidrug resistance of hepatocarcinomas by inhibiting the function of P-gp protein and can enhance the susceptibility of HepG2/ADM cells to cytotoxic drugs.

Objective: To investigate synergistic effect of bromocriptine (BCT) combining tumor necrosis factor-alpha (TNF-alpha) on reversing multidrug resistance in a nude mouse model of liver neoplasm., Methods: Human hepatocarcinoma cell line HepG(2) (HepG(2) group), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (HepG(2)/ADM group) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF (TNF group and BCT group) were injected into the liver of nude mice via orthotopic implantation to establish multidrug resistance model of liver neoplasm in vivo. All the mice were injected with 5-fluouracil + adriamycin + mitomycin in abdominal cavity for 7 d. The mice in BCT group was simultaneously given bromocriptine through gastric canal. Size and weight of the tumor were measured. Furthermore tumor histological character and growth of the nude mice was observed and its chemosensitivity was tested. MDR associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemical staining and reverse transcriptive polymerase chain reaction (RT-PCR), and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay., Results: The nude mouse model of each cell line was all inoculated successfully. The tumor growth rate and weight were significantly different among groups (P < 0.05). After chemotherapy tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups (P < 0.01), and similar to HepG(2) group (54%). MDR1 and LRP mRNA could be detected in all groups, but TNF-alpha was detected only in TNF-alpha and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF-alpha and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups (P < 0.05) with TUNEL assay., Conclusions: TNF-alpha gene can down-regulate the MDR associated genes and proteins expression for example MDR1, LRP, and lower its tumorgenesis. Moreover, bromocriptine can enhance the susceptibility of HepG(2)/ADM cells to cytotoxic drugs.

Objective: To verify the effect of prolactin (PRL) on the development and progression of experimental autoimmune thyroiditis (EAT) in SD rats and the inhibitive effect of bromocriptine (BRC) on the development of EAT., Methods: SD rats were injected with BRC to inhibit the development of EAT and the change of PRL were observed., Results: High level of serum PRL was found in the EAT rats [(8.70 +/- 0.42) microg/L, P < 0.01 vs. control (6.46 +/- 0.67) microg/L], and there was also high levels of thyroid autoantibodies (thyroglobulin antibody, thyroid peroxidase antibody). However, in rats receiving BRC, the levels of thyroid autoantibodies decreased as the PRL level declined (5.30 +/- 0.81) microg/L and the thyroid lesions were mild., Conclusion: Hyperprolactinemia plays a role in the development of EAT and control of the hyperprolactinemia with BRC may afford therapeutic benefit.

Experiments were performed on 31 male SD rats. The results were as follows: (1) The time of waking was increased during the second and third hours after microinjection of 3.3 and 6.6 nmol bromocriptine into bilateral VTA (P < 0.01), but the 1.33 nmol group was without significant effect. (2) The time of waking was decreased during the second and third hours after microinjection of 2 and 4 nmol SCH23390 into VTA (P < 0.01 and P < 0.05 respectively), while 3.4 nmol sulpiride group was without effect. (3) One week after administration of kainic acid (0.3 microgram), the rats presented less time of waking in the day (P < 0.05), while sleep-wakefulness cycle at night showed no change. The results suggest that bromocriptine could increase wakefulness by activating VTA DA neurons via D1 receptor and that the DA neurons might exert a tonic effect for maintaining the wakefulness at the daytime.

This article reports the effect of dopamine (DA) and its agonist bromocriptine (CB154) on the secretion of growth hormone (GH) by pure GH-secreting pituitary tumor in cell culture as well as a comparison of the effects of these dopaminergic drugs and SMS201-295 (SMS). DA of 10(-8) and 10(-7) mol/L reduced GH secretion to 50.6 and 44.4% of the control, respectively, in 1 out of 6 tumors. CB154 of 10(-7) and 10(-6) mol/L suppressed GH secretion to 59.0 +/- 8.9% of the control in 3 out of 4 tumors. CB154 was at least 10 times less potent than SMS vis a vis GH secretion. CB154 of 10(-6) mol/L inhibited GH secretion to 63.3 +/- 13. 8% (n = 4), but SMS of 10(-7) mol/L induced GH secretion to 45.5 +/- 13.1% (n = 4), the concentration difference between CB154 and SMS was 10 times. CB154 suppressed not only GH secretion, but also GH synthesis in two tumor cell cultures. The major role of SMS in GH secretion was inhibition. The results suggest that DA and CB154 have direct inhibitory effects on GH secretion, at least in some pure pituitary GH secreting tumors. The activities of DA and CB154 are not entirely the same as that of SMS.