Abstract: Objective Using pullulan-spermine (Ps) as a carrier of NOTCH1 siRNA to find the effect of NOTCH1 silencing mediated by Ps combined with lysosomal penetration enhancer desloratadine (DL) on acute T lymphocytic leukemia cell line Jurkat. Methods A dynamic light scattering instrument was used to analyze the particle size and Zeta potential of siRNA/Ps complexes with different N/P ratios. Jurkat cells were incubated with siNOTCH1/Ps for 6 hours, then the medium was refreshed with RPMI 1640 complete medium containing 10 μmol/L DL and incubated for another 18 hours, real-time fluorescent quantitative PCR was used to detect the silencing efficiency of NOTCH1; flow cytometry was used to detect the cell cycle and apoptosis; Western blot was used to detect the expres- sion of C-MYC protein, which was the downstream of NOTCH1, and the expression of apoptosis-related proteins caspase 3 and cleaved caspase 3. Results The particle size of siRNA/Ps with N/P ratio of 5 was (203.97±1.07)nm, the zeta potential was (46.13±0.07)mV, and the particles were stable in 10% FBS medium. In Jurkat cells, compared with the no DL group, the siNOTCH1/Ps combined with 10 μmol/L DL induced cell cycle arrest in G₁ phase and promoted cell apoptosis (P＜0.05). At the same time, the expression level of cleaved caspase 3 protein in Jurkat cells increased, the expression level of C-MYC and caspase 3 protein decreased (P＜0.05). Conclusions Ps combined with lysosomal penetration enhancer DL effectively mediates the silencing of NOTCH1 in Jurkat cell, thereby inducing the G₁ phase arrest of acute T lymphocyte leukemia cells and promoting cell apoptosis.

Key words: NOTCH1, spermine-pullulan, desloratadine, acute T lymphocyte leukemia cell line Jurkat, apoptosis