Expression of IL-13Ralpha2 in liver cancer cells and its effect on targeted therapy of liver cancer.
OBJECTIVE
Liver cancer is the third leading cause of cancer-related deaths globally. The number of liver cancers diagnosed in the world is increasing at an alarming rate. It is of great significance to find the new targets of the tumor cells and specific medicine. This research investigated the expression of interleukin-13 receptor alpha2 (IL-13Ralpha2) in different liver cancer cell lines and liver cancer tissues, and assessed the cytotoxin DT389-hIL13-13E13K (IL-13 and diphtheria toxin fusion protein) targeted killing effect on liver cancer cells. Based on study above, we further analyzed the function of IL-13Ralpha2 on the targeted liver cancer therapy. The results will provide a novel strategy and an alternative way for liver cancer therapy.


METHODS
The expression of IL-13Ralpha2 in different liver cancer cell lines and tissues were analyzed by RT-PCR and immunohistochemistry. Cytotoxicity assay of DT389-hIL13-13E13K was performed in eight different concentrations in liver cancer cell lines in vitro. At the same time, siRNA-mediated knockdown was introduced to assess the role of IL-13Ralpha2 in liver cancer therapy.


RESULTS
Two out of four tested liver cancer cell lines and 27 out of 33 (81.82%) liver tissues expressed the IL-13Ralpha2. The fusion protein DT(389)-hIL13-13E13K showed a moderate cytotoxicity to the cancer cell line BEL-7402 in vitro, which 50% inhibition (IC(50)) concentration occurred at 1.4 x 10(-5 )M. Besides, the sensitivity to fusion protein DT(389)-hIL13-13E13K was decreased in siRNA-transfected liver cells compared with control ones. These results suggest that IL-13Ralpha2 chain is a specific target for IL-13-directed fusion protein.


CONCLUSIONS
We reported the expression of IL-13Ralpha2 in liver cancer cell lines and tissues as well as investigated the cytotoxin (DT389-hIL13-13E13K) targeted killing efficiency of liver cancer cells and potential role of IL-13Ralpha2 in the cancer treatment.
Hou
Lingling
L
College of Life Sciences and Bioengineering, Beijing Jiaotong University, 100044 Beijing, People's Republic of China. llhou@bjtu.edu.cn
Du
Juan
J
Wang
Jianwei
J
Liu
Yanfeng
Y
Sun
Weimin
W
Zheng
Yanpeng
Y
Zhang
Lishu
L
Hu
Honggang
H
Dai
Xinxian
X
Guan
Weijun
W
Ma
Yuehui
Y
Hong
Tao
T
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053663:Interleukin-13 Receptor alpha2 Subunit; D034741:RNA, Small Interfering