Cancer Res Treat.  2004 Dec;36(6):395-399.

Proteome Analysis of Differential Protein Expression in Cervical Cancer Cells after Paclitaxel Treatment

• Yim EK
• Bae JS
• Lee SB
• Lee KH
• Kim CJ
• Namkoong S
• Um SJ
• Park JS

Abstract

PURPOSE
It is well known that infection with HPV (human papillomavirus) is the main cause of cervical cancer and certain types of HPV are recognized as carcinogens. At present, there is little information regarding the antineoplastic mechanism of paclitaxel against cervical carcinoma cells. We thus tried to analyze differential protein expression and antineoplastic mechanism-related proteins after paclitaxel treatment on cervical cancer cells by using a proteomic analysis and to investigate the mechanism of action. MATERIALS AND METHODS: Using proteomics analysis including 2-DE and MALDI-TOF-MS, we detected the antineoplastic mechanism-related proteins. Then, we performed western blot analysis for apoptosis- and transformation- related proteins to confirm expression patterns derived from proteome analysis after paclitaxel treatment. RESULTS: We identified several cellular proteins that are responsive to paclitaxel treatment in HeLa cells using proteomics methods. Paclitaxel treatment elevated main-ly apoptosis, immune response and cell cycle check point- related proteins. On the other hand, paclitaxel treatment diminished growth factor/oncogene-related proteins and transcription regulation-related proteins. Also, in the HPV-associated cervical carcinoma cells, paclitaxel demonstrated anti-proliferative activity through the membrane death receptor-mediated apoptotic pathway and the mitochondrial-mediated pathway. CONCLUSION: Identification and characterization of functionally modulated proteins involved in anti-cancer regulatory events should lead to a better nderstanding of the long-term actions of paclitaxel at the molecular level and will contribute to the future development of novel therapeutic drug treatments based upon current therapies.

Keyword

Paclitaxel; HPV; Cervical carcinoma; Proteomics; Apoptosis

MeSH Terms

Apoptosis
Blotting, Western
Carcinogens
Cell Cycle
Hand
HeLa Cells
Humans
Membranes
Paclitaxel*
Proteome*
Proteomics
Uterine Cervical Neoplasms*
Carcinogens
Paclitaxel
Proteome

Figure

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  Fig. 1 Dose- and time-dependent inhibitory effect of paclitaxel on cell growth of HeLa cervical carcinoma cells measured by MTT assay.

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  Fig. 2 2-DE and differential protein expression analysis by paclitaxel treatment. Proteins spots marked on the maps were considered differentially expressed and identified by MS.

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  Fig. 3 Western blots of differentially expressed proteins identified from proteomic analysis. (A) Comparison of the proteins (TRAIL, caspase -5 and -8) obtained from HeLa (control) and paclitaxel treated HeLa cells. (B) Comparison of the proteins (bcl-2 and c-myc) obtained from HeLa and taxol treated HeLa cells. β-actin was used to normalize protein loading.

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