Effects of Compound Zhebei Granule () Combined with Doxorubicin on Expression of Specific Surface Antigens in Mice with Transplanted KG-1a Cells

Abstract

Objective: To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells.

Methods: A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flfl anks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m₂•d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺, in KG-1a cell line tumor xenografts were detected by flfl ow cytometry.

Results: Compared with the control and ADM groups, expression of CD34⁺CD38^- in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34⁺CD38^-CD123⁺ in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺ in the two CZG groups decreased (P<0.05).

Conclusions: CZG combined with doxorubicin could reduce the expression of CD34⁺CD38^-, CD34⁺CD38^-CD123⁺, CD34⁺CD38^-CD96⁺ and CD34⁺CD38^-CD33⁺ in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization.

Keywords: Chinese medicine; acute myeloid leukemia; adriamycin; doxorubicin.