Molecular and Cellular Biochemistry

, Volume 348, Issue 1–2, pp 11–19 | Cite as

Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173

  • Lu Kong
  • Zhihong Deng
  • Haiying Shen
  • Yuxiang Zhang


Tyrosine (Y) kinases inhibitors have been approved for targeted treatment of cancer. However, their clinical use is limited to some cancers and the mechanism of their action remains unclear. Previous study has indicated that PP2, a selective inhibitor of the Src family of non-receptor tyrosine kinases (nRTK), efficiently repressed cervical cancer growth in vitro and in vivo. In this regard, our aims are to explore the mechanism of PP2 on cervical cancer cell growth inhibition by investigating the suppressive divergence among PP1, PP2, and a negative control compound PP3. MTT results showed that three compounds had different inhibitory effects on proliferation of two cervical cancer cells, HeLa and SiHa, and PP2 was most efficient in a time- and dose-dependent manner. Moreover, we found 10 μM PP2 down-regulated pSrc-Y416 (P < 0.05), pEGFR-Y845 (P < 0.05), and -Y1173 (P < 0.05) expression levels, while 10 μM PP1 down-regulated pSrc-Y416 (P < 0.05) and pEGFR-Y845 (P < 0.05), but not pEGFR-Y1173; 10 μM PP3 down-regulated only pEGFR-Y1173 (P < 0.05). PP2 could modulate cell cycle arrest by up-regulating p21Cip1 and p27Kip1 in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. Our results indicate that Src pathway and EGFR pathway play different roles in the proliferation of cervical cancer cells and PP2 efficiently reduces cervical cancer cell proliferation by reduction of both Src and EGFR activity.


Cervical cancer Proliferation EGFR Src kinases inhibitor 



Non-receptor tyrosine kinases






Epidermal growth factor receptor


4-Amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine


4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine


4-Amino-7-phenylpyrazol[3,4-d] pyrimidine


Cyclin-dependent kinase


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide



This work was supported by Major State Basic Research Development Programs (2009CB521800; 2010CB529400) and the National Natural Sciences Foundation of China (30672422). We thank Ms. Xingcui Wang for the flow cytometry work.

Conflict of interest


Supplementary material

11010_2010_632_MOESM1_ESM.rtf (44 kb)
Supplementary material 1 (RTF 43 kb)
11010_2010_632_MOESM2_ESM.rtf (37 kb)
Supplementary material 2 (RTF 36 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lu Kong
    • 1
  • Zhihong Deng
    • 1
  • Haiying Shen
    • 1
  • Yuxiang Zhang
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Cancer InstituteCapital Medical UniversityBeijingChina

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