[Enhancement of reversing drug resistance of K562/A02 cells to adriamycin by ultrasound-induced cavitation].
This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.
Chen
Bao-An
BA
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China. cba8888@hotmail.com
Meng
Qing-Qi
QQ
Wu
Wei
W
Gao
Feng
F
Shao
Ze-Ye
ZY
Ding
Jia-Hua
JH
Gao
Chong
C
Sun
Xin-Chen
XC
Cheng
Hong-Yan
HY
Sun
Yun-Yu
YY
Wang
Jun
J
Cheng
Jian
J
Zhao
Gang
G
Song
Hui-Hui
HH
Bao
Wen
W
Ma
Yan
Y
Wang
Xue-Mei
XM
D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D014465:Ultrasonics
D004317:Doxorubicin