Abstract: Li Zhouna, Chen Xiangru, Jin Zhehu Department of Dermatology, Yanbian University Hospital, Yanji 133000, Jilin, China Corresponding author: Jin Zhehu, Email: jinzh_621@163.com 【Abstract】 Objective To evaluate effects of 4?hydroxyphenyl retinamide （4?HPR） in different vehicles on the proliferation and apoptosis of human keloid fibroblasts （HKFs）. Methods A film?ultrasonic dispersion method was used to prepare 4?HPR liposome solution and 4?HPR microbubbles. Primary HKFs were in vitro treated with the 4?HPR liposome solution at different concentrations of 0 - 80 mg/L for 6 - 48 hours, and the proliferative activity of HKFs was evaluated by methyl thiazolyl tetrazo?lium （MTT） assay. Some other HKFs were divided into 3 experimental groups to be treated with 15 mg/L 4?HPR solution （4?HPR solution group）, 15 mg/L 4?HPR liposome solution （4?HPR liposome solution group） and 15 mg/L 4?HPR microbubbles （4?HPR microbubble group）, respectively, and each group was divided into ultrasonic?treated and ?untreated subgroups. HKFs without treatment served as control group. After 24?hour treatment, MTT assay was conducted to evaluate the proliferative activity of HKFs in the above groups, flow cytometry to detect apoptosis of HKFs in all groups except the 4?HPR solution group. Results The 4?HPR liposome solution and 4?HPR microbubbles were successfully prepared. MTT assay showed inhibitory effects of 4?HPR liposome solution at concentrations of 1 - 80 mg/L on the proliferation of HKFs, and the proliferation inhibition rate was positively associated with the drug concentrations （r = 0.633, P < 0.01）. After the ultrasonic treatment, inhibitory effects on the proliferation of HKFs significantly differed among the 4?HPR microbubble group, 4?HPR solution group and 4?HPR liposome solution group （P < 0.01）. The 4?HPR liposome solution group and the 4?HPR microbubble group both showed significantly increased apoptosis rates （21.81% ± 3.73%, 39.79% ± 1.61%, respectively） compared with the control group （6.18% ± 0.61%, both P < 0.01）. Conclusion The 4?HPR microbubbles are successfully prepared, and 4?HPR in different vehicles all can promote HKF apoptosis and suppress HKF proliferation, among which, 4?HPR microbubbles in combination with ultrasonic treatment have stronger inhibitory effects than the 4?HPR liposome solution.