[Dual regulation of cell cycles by Shuanghuang Shengbai Granule in Lewis-bearing mice with chemotherapy-induced myelosuppression and its mechanism].
OBJECTIVE
To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression.


METHODS
Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewis-bearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method.


RESULTS
Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G0/G1 phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G0/G1 phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyclin D1 in tumor tissues were decreased as compared with the untreated and control groups.


CONCLUSIONS
Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.
Wang
Li-fang
LF
Cancer Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Division of Cancer Research, Shanghai Chest Hospital, Shanghai 200032, China.
Xu
Zhen-ye
ZY
Jin
Chang-juan
CJ
Sha
Hui-fang
HF
Wang
Zhong-qi
ZQ
Zhou
Wei-dong
WD
Zhang
Ming
M
Wu
Ji
J
Bai
Bing
B
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D011897:Random Allocation
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D019938:Cyclin D1; D003520:Cyclophosphamide; D051358:Cyclin-Dependent Kinase 4