Preparation of curcumin TPP-PEG-PE nanomicelles with mitochondrial targeting and lysosomal escape functions and its effect on promoting breast cancer cell apoptosis / 中国中药杂志

Orthogonal experiments were used to optimize the process parameters of curcumin TPP-PEG-PCL nanomicelles; the particle size, electric potential and morphology under the electron microscope were systematically detected for the curcumin TPP-PEG-PCL nanomicelles; and the stability and in vitro release of the curcumin TPP-PEG-PCL nanomicelles were investigated. With DID fluorescent dye as the fluorescent probe, flow cytometry was used to study the uptake of nanomicelles by breast cancer cells, and laser confocal microscopy was used to study the mitochondrial targeting and lysosomal escape functions of nanomicelles. Under the same dosage conditions, the effect of curcumin TPP-PEG-PCL nanomicelles on promoting the apoptosis of breast cancer cells was evaluated. The optimal particle size of curcumin TPP-PEG-PCL nanomicelle was(17.3±0.3) nm, and the Zeta potential was(14.6±2.6) mV in orthogonal test. Under such conditions, the micelle appeared as regular spheres under the transmission electron microscope. Fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote drug uptake by tumor cells, escape from lysosomal phagocytosis, and target the mitochondria. The cell survival rate and Hoechst staining positive test results showed that curcumin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of breast cancer cells. The curcumin TPP-PEG-PCL micelles can significantly reduce the mitochondrial membrane potential of breast cancer cells, increase the release of cytochrome C, significantly increase the expression of pro-apoptotic protein Bcl-2 and reduce the expression of anti-apoptotic Bax protein. These test results were significantly better than those of curcumin PEG-PCL nanomicelles and curcumin, with statistically significant differences. The results revealed that curcumin TPP-PEG-PCL nanomicelles can well target breast cancer cell mitochondria and escape from the lysosomal capture, thereby enhancing the drug's role in promoting tumor cell apoptosis.

A Preliminary Study on the Role of Mitochondrial Protein, Bcl-2 and Bax in Tumorigenesis / 中国肿瘤临床

Objective: To study the expressions of mitochondrial protein (MAB1273), Bcl-2, and Bax in renal cell carcinoma and to investigate their role in the tumorigenesis. Methods: The expressions of mitochondrial protein, Bcl-2 and Bax were detected by immunohistochemistry SP method in 9 tissue samples of renal on-cocytoma, 6 samples of chromophobe carcinoma, 23 samples of clear cell carcinoma and 12 samples of normal renal tissue. Results: The expression of MAB1273 in renal oncocytoma, chromophobe carcinoma and clear cell carcinoma was much higher than that in normal renal tissue (P=0.006). No significant difference was found in MAB1273 expression among the three types of renal carcinoma. The expression of Bcl-2 was higher in the renal carcinoma groups than in the normal renal tissue group, with a significant difference (P=0.008). The expression of Bax was not different among all of the groups (P=0.057). Rank correlation analysis showed a positive correlation between MAB1273 and Bcl-2 expression (r=0.341, P=0.015). The expression of Bcl-2 was negatively correlated with Bax expression (r= -0.287, P=0.043). Conclusion: Overexpression of mitochondrial protein and Bcl-2 and underexpression of Bax may play a part in the genesis of renal oncocytoma, chromophobe carcinoma and the clear cell carcinoma, indicating that overexpression of MAB1273 may be correlated with apoptosis of renal cell carcinoma cells.