Chimeric antibody targeting SRPK-1 in the treatment of non-small cell lung cancer by inhibiting growth, migration and invasion

Wu,Fan; Li,Jie; Du,Xin; Zhang,Weisan; Lei,Ping; Zhang,Qiang

doi:10.3892/mmr.2017.6833

Chimeric antibody targeting SRPK-1 in the treatment of non-small cell lung cancer by inhibiting growth, migration and invasion

Authors:
- Fan Wu
- Jie Li
- Xin Du
- Weisan Zhang
- Ping Lei
- Qiang Zhang
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Affiliations: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/mmr.2017.6833
Pages: 2121-2127

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Abstract

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in humans, and is characterized by rapid growth, migration, invasion and reoccurrence. Evidence has indicated that the protein and mRNA levels of serine‑arginine protein kinase‑1 (SRPK‑1) are upregulated in NSCLC tissues. However, the functions of SRPK1 and targeted therapy for SRPK1 in the progression and treatment of NSCLC remain to be fully elucidated. In the present study, the mRNA and protein expression levels of SRPK‑1 in NSCLC cells and tissues were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis and SDS‑PAGE, and the role of SRPK1 in the progression of NSCLC was investigated. In addition, a chimeric antibody target for SRPK‑1 (ChanSRPK‑1) was constructed, and the therapeutic effects of ChanSRPK‑1 were investigated in H358‑bearing mice. The curative effects of ChanSRPK‑1 on the inhibition of growth, migration and invasion of NSCLC were also examined in vitro and in vivo. The results revealed that the mRNA and protein levels of SRPK‑1 were upregulated in NSCLC cells and tumor tissues. Higher expression of SRPK1 promoted NSCLC cell growth, migration and invasion, whereas lower expression of SRPK‑1 suppressed growth, migration and invasion of the NSCLC cells. Animal experiments demonstrated that ChanSRPK‑1 inhibited the β‑catenin/T‑cell factor complex. ChanSRPK‑1 treatment also downregulated the phosphorylation levels of glycogen synthase kinase 3-β and prolonged the survival of tumor‑bearing mice. Taken together, SRPK‑1 may offer potential as a therapeutic target oncogenic molecular in NSCLC, and ChanSRPK‑1 may be a therapeutic agent with functions as a target and for oncolytic therapy in the treatment of NSCLC.

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