title: Enhanced chemosensitivity to CPT-11 in colorectal carcinoma xenografts  by small hairpin RNA interference targeting PLK1.
abstract: Commonly used drugs for the treatment of colon{} cancer patients like CPT-11 shows severe side effects or induces resistance in clinical settings. Thus, we analyzed a combination of PLK1 (polo-like kinase 1)-specific short hair RNA (shRNA), a potent tool to destroy mitosis in cancer cells, together with CPT-11 to enhance drug sensitivity. Cellular proliferation and apoptosis were determined in SW620 colorectal carcinoma cells. Knockdown of cellular PLK1 led to the decreased mRNA and PLK1 protein in RT-PCR and western blot assay. The viability declined (p<0.001) in MTT assay and colony formation assay, and the number of apoptotic cells was clearly increased (p<0.01) in flow cytometric analysis and Hoechst 33258 staining compared with control cells after incubation with PLK1-specific shRNA and SN-38. We found the level of cleaved PARP was also increased in vitro. In vivo, employment of shRNA targeting PLK1 improved the sensitivity to treat SW620 nude mouse model toward CPT-11. The combination therapy inhibited cellular proliferation and promoted apoptosis observed at the percentage of PCNA and caspase3 by immunohistochemistry, accompanied with TUNEL assay. As we expect, the combination treatment delayed tumor growth (p<0.01) and simultaneously reduced tumor weight (p<0.01) compared with control group. Taken together, combination of PLK1-specific shRNA interference with low-dose CPT-11 triggered a antitumor efficacy and represented a potential strategy to treat colon cancer.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Ke-yuan Road 4, No. 1, Gao-peng Street, Chengdu, Sichuan, 610041, China.
authors.forename: P
authors.initials: P
authors.lastname: Fan
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Tian
authors.forename: N
authors.initials: N
authors.lastname: Yan
authors.forename: L
authors.initials: L
authors.lastname: Dai
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: H
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D018797:Cell Cycle Proteins; D000077146:Irinotecan; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1