Ginsenoside metabolite compound K enhances the efficacy of cisplatin in lung cancer cells.
OBJECTIVE
To evaluate the potential of ginsenoside metabolite compound K (CK) in enhancing the anti-tumor effects of cisplatin against lung cancer cells, including cell proliferation and apoptosis, and the underlying mechanism.


METHODS
Western blotting and p53 reporter assay were used to assess p53 expression and activity. MTT assay and TUNEL staining were employed to investigate the drug effects on cell growth and apoptosis, respectively. Combination index (CI) was calculated to determine synergism.


RESULTS
We found that CK could significantly enhance cisplatin-induced p53 expression and activity in two lung cancer cell lines, H460 and A549. Consequently, synergistic inhibition of cell growth was observed when the cells were co-treated with CK and cisplatin compared to single treatment. In addition, the ability of cisplatin in apoptosis induction was similarly synergized by CK. Furthermore, by using p53-null lung cancer cells, we demonstrate that the synergy was p53 dependent.


CONCLUSIONS
Conventional chemotherapies are often accompanied by development of drug resistance and severe side effects. Novel discoveries of low toxicity compounds to improve the outcome or enhance the efficacy of chemotherapies are of great interest. In the present study, our data provide the first evidence that CK could be potentially used as an agent to synergize the efficacy of cisplatin in lung cancer.
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Yang
Y
Li
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Tong
T
Zhou
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Chengyuan
C
Ma
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Weiwei
W
Song
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Jian
J
Zhang
1 Department of Respiration, 2 Department of Endocrinology, 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun 130021, China ; 4 Center of Diagnosis and Treatment of Respiratory and Allergic Diseases, The General Hospital of Shenyang Military Command, Shenyang 110015, China ; 5 Department of Pleurisy, Changchun Infectious Disease Hospital, Changchun 130031, China.
Zhenxiang
Z
Yu
Compound K (CK); cisplatin; ginsenoside; lung cancer