Annals of Coloproctology

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Change in Expression of Survivin Caused by Using Oxaliplatin in HCT116 Colon Cancer Cells: Won Jun Sohn, Jung Won Lee, Dong-Guk Park; J Korean Soc Coloproctol. 2010;26(4):246-253. Published online August 31, 2010; DOI: https://doi.org/10.3393/jksc.2010.26.4.246

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Purpose

Oxaliplatin is a third-generation platinum compound, and it has no nephrotoxicity and has reduced bone marrow toxicity. Cancer cells that are resistant to cisplatin are sensitive to oxaliplatin. Oxaliplatin is used widely for the treatment of colon cancers. Recently, oxaliplatin was reported to inhibit the expression of survivin, which protects cell apoptosis. However, there are no reports on the expressions of survivin variants and the changes in intracellular localization of survivin in cancer cells. We studied the expression of survivin caused by oxaliplatin in HCT116 colon cancer cells, and we observed the localization of survivin in the mitotic phase.

Methods

We treated the HCT116 colon cancer cells with 2.0 µM of oxaliplatin, and we studied the expressions of survivin protein, and survivin mRNA variants, as well as the changes in intracellular localization, by using the Western blot method, RT-PCR, immunocytochemistry, and flowcytometry.

Results

Oxaliplatin inhibits the expression of the survivin protein and survivin mRNA in HCT116 colon cancer cells. The expression of the survivin-2B variants, which have no antiapoptotic activity but control cell mitosis by localization on a microtubule, is reduced continuously 2 days after treatment with oxaliplatin. In immunocytochemistry, expression of survivin in the cytoplasm is reduced and especially is not expressed in microtubules and contractile rings.

Conclusion

One of the mechanisms of oxaliplatin is to inhibit the expression of and to change the localization of survivin. Based on these results, we suggest that changes in the expression of survivin variants and in their localization are two effects of oxaliplatin.

Citations

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Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial
M Verstraete, A Debucquoy, J Dekervel, J van Pelt, C Verslype, E Devos, G Chiritescu, K Dumon, A D'Hoore, O Gevaert, X Sagaert, E Van Cutsem, K Haustermans
British Journal of Cancer.2015; 112(8): 1314. CrossRef
Antichemosensitizing effect of resveratrol in cotreatment with oxaliplatin in HCT116 colon cancer cell
Dong-Guk Park
Annals of Surgical Treatment and Research.2014; 86(2): 68. CrossRef

Pathological Analysis of Tumor Response after Preoperative Chemoradiation Therapy for Advanced Rectal Cancer.: Lee, Seok Young , Choi, Yoon Jung , Kang, Jung Gu , Chung, Eun Ji , Kim, Yong Tai; J Korean Soc Coloproctol. 2007;23(6):511-517.; DOI: https://doi.org/10.3393/jksc.2007.23.6.511

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Abstract PDF

PURPOSE
We investigated the association of survivin expression with the prognosis in advanced rectal cancer with preoperative chemoradiotherapy for pathological analysis.
METHODS
We examined 16 patients with rectal cancer who were preoperatively staged as T3 or T4. The enrolled patients were given 5-FU, 425 mg/m2/day, and leucovorin, 20 mg/m2/day, intravenously for 3 days during weeks 1 and 5 of pelvic radiotherapy. Surgical resection was performed 4~6 weeks after completion of the schedule. Tumor response was divided into CR (complete remission), PR (partial remission), and NR (non remission). Immunohistochemical staining of paraffin sections using monoclonal antibodies for survivin, bcl-2, and p53 was performed on pretreatment biopsy and surgically resected tissue by using the standard avidin-biotin-peroxidase technique.
RESULTS
No CR was achieved. PR was achieved in 10 patients (62.5%), and NR in 6 patients (37.5%). After preoperative treatment, survivin expression tended to be decreased in tumor cells (62.5% to 31.3%) and slightly increased in adjacent normal mucosa a (12.5% to 25%). After preoperative treatment, survivin expression was correlated with lymph-node metastasis in the statistical analysis. We failed to find any other significant relationship between survivin expression and any parameters, except lymph node metastasis and apoptotic index.
CONCLUSIONS
Survivin expression before preoperative treatment was not related to the prognosis in rectal cancer patients, but survivin expression after preoperative treatment was related to lymph node metastasis of advanced rectal cancer. Further studies, including large numbers of rectal cancer cases with a sufficient follow-up period, are needed in order to establish survivin as a prognostic target in rectal cancer.

Citations

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Clinicopathologic significance of survivin expression in colorectal adenocarcinoma
Woong Na, Se Min Jang, Young Jin Jun, Young Soo Song, Ki‐Seok Jang, Kang Hong Lee, Kyeong Geun Lee, Hong Xiu Han, Seung Sam Paik
Basic and Applied Pathology.2009; 2(3): 94. CrossRef

Expression of Survivin and Its Correlation with Prognosis in Colorectal Cancer.: Baek, Moo Jun , Lee, Eung Min , Kim, Chang Jin , Park, Nae Kyung , Shin, Eung Jin , Jang, Yong Seog , Kim, Jae Jun , Kim, Sung Yong , Lee, Moon Soo , Kim, Chang Ho , Song, Ok Pyung; J Korean Soc Coloproctol. 2006;22(2):125-131.

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Abstract PDF: PURPOSE
Survivin is involved in both the control of cell division and the inhibition of apoptosis. Specifically, its anti-apoptotic function is related to the ability to inhibit caspases directly or indirectly. This study examined the expression patterns of survivin in normal colorectal tissues and in colorectal cancer tissues to determine whether the expression of survivin is associated with either the colorectal cancer characteristics or the prognosis.
METHODS
4micrometer sections of the formalin-fixed paraffin-embedded samples of colorectal cancer tissues were the immunostained using antibodies for survivin. The immunostain was recorded as 0~3 depending on the stain intensity distribution in the cytoplasm and the nucleus.
RESULTS
Survivin was localized in the nucleus and/or cytoplasm of tumor cells. We could differentiate between cytoplasmic and nuclear localization of survivin protein expression. Among the cancer expressions, 35.8% demonstrated nuclear staining, and 51.9% demonstrated cytoplasm staining. Statistical analysis revealed that cytoplasmic survivin expression was correlated with lymph-node metastasis, tumor stage, and patient survival.
CONCLUSIONS
Survivin expression was correlated with clinicopathologic prognostic parameters and with the outcome. Thus, it can be both a useful diagnostic marker for colorectal carcinomas and an important source of prognostic information for patients with a colorectal carcinoma. Survivin will become a potential new target in anti-cancer therapy in near future.

Western Blotting to Assess the Expression of Survivin in Colorectal Cancer.: Kang, Sung Ku , Lee, Ryung Ah , Kim, In Kyoung , Moon, Sun Mi , Hwang, Dae Yong; J Korean Soc Coloproctol. 2003;19(6):386-390.

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Abstract PDF: PURPOSE
The balance between cell death and proliferation is a key step in cellular homeostasis. Inhibition of apoptosis could trigger an abnormal malignant change. Survivin is a recently reported anti-apoptotic molecule that inhibits the caspase system along the apoptosis pathway. It is expressed in fetal tissue and transformed tissue, but not in normal tissues except durung the mitosis period. Some authors have described abnormal survivin expression in various cancer tissues. We performed western blotting in colorectal cancer to assess the expression pattern of survivin.
METHODS
Thirty-four colorectal cancer tissues and adjacent normal colonic epithelia of patients operated an at KCCH from June 1998 were assessed. We used the common western blotting method with the polyclonal anti-survivin antibody.
RESULTS
Survivin was expressed in all cases (34 cases, 100%) of cancer tissues and two cases (5.8%) of normal tissue. Seven of 34 cases showed a strong positive result. Univariate analysis of sex, age, stage, original site, lymphatic invasion, neural invasion, and vessel invasion between the positive group and the strongly positive group revealed no significant relationship except for neural invasion.
CONCLUSIONS
Survivin should be a good tumor marker of colorectal cancer.

Expression of Survivin in Human Colorectal Cancer Tissues.: Lee, Ryung Ah , Kim, Kwang Ho , Shim, Kang Sup; J Korean Soc Coloproctol. 2000;16(3):131-138.

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Abstract PDF: Survivin, the recently discovered apoptosis inhibitor of inhibitor of apoptosis (IAP) family is located in chromosome 17q25. It is found only in fetal tissue and transformed tissue but is never found in normal adult tissue. Several authors reported survivin expression in various cancer tissues, which suggested the role of survivin in cancer development. This study intended to find the degree of survivin expression making use of RT-PCR technology and to compare the expression pattern of survivin, caspase 3, and PARP.
METHODS
The cell lines known to have survivin expression such as HL60, Daudi, THP1, and colon cancer cell lines such as COLO 201, WiDr and breast cancer cell line ZR-75-1 were used for the positive control. For the negative control, normal colon tissues were included. The total RNAs from the frozen tissue of 6 normal colon, 36 specimens of colorectal cancer, and cell lines were used in RT-PCR. The 20 paraffin embedded tissues were used in immunohistochemical study in order to find out the degree of protein expression of caspase 3 and PARP. Western blotting was conducted on same tissues for caspase 3 as usual manners.
RESULTS
The survivin expression by RT-PCR techniques was found in the 22 cases (61.1%). As a result of the immunohistochemical staining, 13 cases (65%) in caspase 3, 17 cases (85%) in PARP showed reduced staining. In western blotting, 32 kDa inactive form of caspase 3 was expressed in 16 cases (80%), but the band of active split form was not found. No significant relationship was found between survivin expression and clinicopathologic data of colorectal carcinomas, and expression of caspase 3 and PARP.
CONCLUSIONS
These result suggest that apoptosis mechanism is depressed in colorectal cancer tissues and survivin plays a role in the inhibition of apoptosis of colorectal cancer. More profound study could confirm the apoptosis mechanism in tumorigenesis.

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