RESUMO
To study the reversal effect of docetaxel (DTX) and verapamil (VRP) liposome (DTX-VRP LP) on multidrug resistance of human breast cancer chemotherapy, DTX-VRP LP was prepared by thin film dispersion method. The particle size and zeta potential were measured by laser particle sizer. The drug loading, entrapment efficiency and the cumulative release rate of liposomes in phosphate buffer saline solution (PBS) with pH 7.4 and 6.8 were determined by ultrafiltration and dynamic dialysis, respectively. With DTX resistant human breast cancer cells (MCF-7/DTX) to study on the pharmacodynamics of liposomes in vitro and in vivo. The animal experiments were approved by the Animal Research Ethics Committee of School of Medicine of Shanghai Jiao Tong University (No. 2019-06-172). The average particle size and zeta potential of DTX-VRP LP were about 140.9 nm and -28.7 mV, respectively. The entrapment efficiency and drug loading of DTX and VRP in DTX-VRP LP were (81.7 ± 3.9)%, (2.9 ± 0.3)% and (59.6 ± 0.6)%, (1.6 ± 0.5)%, respectively. The cumulative release rate of the group of DTX-VRP LP was about 40% and 70% within 0-4 h in pH 7.4 and 6.8 PBS, respectively. It was slightly slower compared with other experimental groups. In vitro pharmacodynamics experiments, the value of IC50 of DTX solution, DTX LP and DTX-VRP LP were 3.19 ± 0.6, 1.46 ± 0.48 and 1.12 ± 0.33 μmol·L-1 on human breast cancer cells (MCF-7), respectively. The results showed the data was not much difference between the other groups and all experimental groups had strong cytotoxicity on MCF-7. However, on the MCF-7/DTX, the IC50 values of the other groups were greater than 10 μmol·L-1 while DTX-VRP LP group 7.4 ± 2.86 μmol·L-1. The results showed DTX-VRP LP had obvious cytotoxicity with the concentration dependent reversal of multidrug resistance (MDR) of breast cancer MCF-7/DTX cells (P<0.05), the other experimental groups had no effect on MCF-7/DTX cells. The inhibitory effect of MCF-7/DTX in vivo is consistent with that in vitro. In conclusion, DTX-VRP LP could reverse the MDR of MCF-7/DTX cells.
RESUMO
<p><b>BACKGROUND</b>The effects of triterpenic acid from Prunella vulgaris L. (TAP) on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin (STZ)-diabetic rats.</p><p><b>METHODS</b>The diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose ≥ 16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups: (1) Diabetes rat (STZ), (2) Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L (STZ + TAP50), (3) Diabetic rats treated with 100 mg/kg TAP (STZ + TAP100), and (4) Diabetic rats treated with 200 mg/kg TAP (STZ + TAP200). Normal rats (n = 10) acted as the control group (NC). TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose (BG) were measured after three and six weeks. Fructosamine (FMN), malondialdehyde (MDA), and nitric oxide (NO), and the activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD) in serum were determined after six weeks using commercially available kits following the manufacturer's instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin (HE) staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group (P < 0.01). The activity of SOD in serum and the body weight was significantly decreased compared with the control group (P < 0.01). After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells.</p><p><b>CONCLUSIONS</b>Triterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.</p>