ABSTRACT
Objective To verify the synergistic effect of transferrin modified β-elemene and celastrol co-loaded microemulsion (Tf-EC-MEs) on anti-colorectal cancer treatment. Methods The optimal mass ratio of β-elemene and celastrol to growth inhibition of Lovo and HT-29 colorectal cancer cells was optimized by MTT staining method in vitro. Tf-EC-MEs was prepared by “mixing-dripping” method, and the preparation and physicochemical properties of the particles were characterized by high performance liquid chromatography (HPLC), laser particle analyzer, and transmission electron microscope. The MTT staining, HPLC-BCA combined method, and Annexin V-PE/7-Aminoactinomycin D (Annexin V-PE/7-AAD) kit were used to investigate the antitumor activity of Tf-EC-MEs in vitro, and its effect on cell uptake, and apoptosis of tumor cells. The tumor-bearing nude mice model was established by subcutaneous injection of Lovo cells, and the tumor growth, weight, and survival time were observed after intravenous injection of β-elemene + celastrol, β-elemene-celastrol co-loaded microemulsion (EC-MEs), and Tf-EC-MEs. Results The combined administration of β-elemene and celastrol (40:1) had significant synergistic effect on the anti-colorectal cancer of Lovo and HT-29 cells. IC50 of β-elemene + celastrol in Lovo and HT-29 cells were (17.5 ± 2.9) and (36.4 ± 3.6) μg/mL, with the CI as 0.89 and 0.96, respectively. IC50 of Tf-EC-MEs in Lovo and HT-29 cells were (11.7 ± 0.6) and (27.4 ± 1.2) μg/mL, with the CI as 0.61 and 0.72 respectively. The 4 h of Lovo uptake of Tf-EC-MEs was 7.2 μg/mg, which was 3.3 times higher than that of β-elemene + celastrol. Tf-EC-MEs induced apoptosis in 59.2% of Lovo cells, which was significantly higher than that in beta-elemene + celastrol and EC-MEs groups. Tf-EC-MEs showed the overwhelming inhibition of growth of Lovo tumor-bearing tumors. The survival rate of Tf-EC-MEs-treated mice was 37.5% at day 60. In Tf-EC-MEs treated group, HE staining sections of tumor tissues showed substantial cell necrosis and the Ki-67 immunohistochemical sections displayed the significant inhibition of proliferation of tumor cells. Conclusion Compared with the combination group (beta-elemene and celastrol) and EC-MEs groups, Tf-EC-MEs has a promising potential in the synergistic anti-colorectal cancer treatment.
ABSTRACT
Pancreatic cancer has one of the worst prognoses among all types of cancers. The survival rate is less than 5 per cent; this is due to difficulty in diagnosing at an early stage. Despite the improvements in diagnostic imaging techniques such as computed tomography, magnetic resonance imaging, etc., the early diagnosis of pancreatic cancer is still difficult. Alternative methods of diagnosing pancreatic cancer at an early stage are presently been explored. The detection of telomerase activity has been proposed to be a useful tool in the diagnosis of pancreatic cancer. Telomerase is made up of three major parts namely, human telomerase reverse transcriptase, human telomerase and telomerase -associated protein. Several researchers have shown telomerase activity in tissues and fluids of patients with pancreatic and other types of cancers. About 95 per cent telomerase activity has been detected in pancreatic adenocarcinoma. Since telomerase activity is present in a vast majority of human cancers, it might have a role in the diagnosis and treatment of cancer.