Identification of cervical cancer proteins associated with treatment with paclitaxel and cisplatin in patients.

Abstract

OBJECTIVE:

Neoadjuvant chemotherapy (NAC) with paclitaxel (T) and cisplatin (P) was commonly used for the treatment of cervical cancer. However, little is known about the antineoplastic mechanism of NAC with TP in patient tissues in situ. In this study, we compared the proteomic profiles of cervical cancer in patients before and after NAC with TP to identify proteins that may shed light on the mechanism of TP action.

METHODS:

We collected cervical cancer tissues pre- and post-NAC with TP from 6 patients with local advanced cervical cancer and stored them at -80°C. Proteomes of 2 groups of cervical cancer tissues were analyzed by 2-dimensional gel electrophoresis and the differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. Some proteins that are differentially expressed were confirmed by Western blot.

RESULTS:

There were 13 proteins whose levels were significantly altered after NAC with TP. Compared with pre-NAC, 11 proteins were down-regulated, and 2 proteins were up-regulated in the post-NAC group. The down-regulated proteins were aldolase A, pyruvate kinase, enolase 1, heat shock protein 27 (HSP27), HSP70, actinin α1, lamin B1, eukaryotic translation elongation factor 1γ, annexin 1, epithelial cell marker protein1, keratin II-type. In contrast, apolipoprotein A1 and annexin V were up-regulated. The down-regulation of HSP27, HSP70, enolase 1, and aldolase A was verified by Western blot.

CONCLUSIONS:

Differentially expressed proteins between cervical cancer tissues pre- and post-NAC with TP were identified by comparative proteomic approach. The NAC therapy with TP down-regulated proteins involved in energy production (glycolytic enzymes) and chaperones but up-regulated proteins involved in apoptosis. These findings shed new light on biomarkers associated with effect of chemotherapy.

• Authors: Huiling Liu, Yin Han, Ruoran Mi, Ying Zhang, Gang Su, Hailin Wang, Xin Zhou, Xiangwen Liu, Bingdong Zhu
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 21 Issue 8 Pg. 1452-7 (Nov 2011) ISSN: 1525-1438 [Electronic] England
• PMID: 22027750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Neoplasm Proteins
• Paclitaxel
• Cisplatin

Topics

• Antineoplastic Agents (therapeutic use)
• Blotting, Western
• Carcinoma, Squamous Cell (drug therapy, metabolism)
• Chemotherapy, Adjuvant
• Cisplatin (therapeutic use)
• Female
• Humans
• Neoplasm Proteins (metabolism)
• Paclitaxel (therapeutic use)
• Proteomics
• Uterine Cervical Neoplasms (drug therapy, metabolism)