Combination of SL327 and Sunitinib Malate leads to an additive anti-cancer effect in doxorubicin resistant thyroid carcinoma cells.
BACKGROUND
Receptor tyrosine kinases (RTKs) play crucial roles in numerous cancer cell processes including cell survival, proliferation, and migration. MEK1/2 MAPK kinases are very important for cancer survival and development. Anaplastic thyroid carcinoma (ATC) is a deadly type of thyroid cancer and there are no very effective systemic treatment strategies for ATC so far. Also, ATC can easily become resistant to therapy of traditional therapeutic drugs for ATC, such as doxorubicin. Drug combination treatment could be a promising therapeutic strategy for ATC, especially for drug resistant ATC.


METHODS
We explored the combination effect between a MEK1/2 inhibitor SL327 and a multi-targeted RTK inhibitor Sunitinib Malate in doxorubicin resistant ATC cells using cell viability assay, cell migration assay, nuclei morphology and caspase-3 activity analysis, as well as in vivo tumor growth assay.


RESULTS
There is a significant additive effect between SL327 and Sunitinib Malate in reducing viability, increasing apoptosis, and suppressing migration of doxorubicin-resistant ATC cells. Importantly, combination of SL327 and Sunitinib Malate induced significant additive suppression of in vivo doxorubicin-resistant ATC tumor growth.


CONCLUSIONS
Our results suggest that the combination of MEK1/2 inhibitor and RTK inhibitor is promising for treatment of ATC especially doxorubicin-resistant ATC. The combination might not only enhance the anti-cancer efficacy, but also reduce the side effects and overcome drug resistance developed in ATC treatment. All these might provide useful information for clinical therapeutics of ATC.
Department of Endocrine, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Shandong, 264000, PR China.
Wei
W
Wang
Department of Endocrine, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Shandong, 264000, PR China.
Jin
J
Zhou
Department of Hemodialysis, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Shandong, 264000, PR China.
Lujie
L
Zhao
Department of Endocrine, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Shandong, 264000, PR China. Electronic address: shulin_ch@163.com.
Shulin
S
Chen
D000607:Aminoacetonitrile / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008819:Mice, Nude; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C424127:SL 327; D043823:Taxoids; D000077143:Docetaxel; D000607:Aminoacetonitrile; D004317:Doxorubicin; D053148:Caspase 3; D000077210:Sunitinib
Cell migration; Cell viability; Doxorubicin; Resistance; Thyroid carcinoma