Assessment of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with oral cavity cancer.

BACKGROUND: Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. METHODS: We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. RESULTS: A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p < 0.001) and clinical stage (p = 0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively. CONCLUSIONS: The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Tracking the dropout patients of neoadjuvant chemotherapy with locally advanced oral cavity cancer.

BACKGROUND: Patients with locally advanced oral cavity cancer sometimes stopped treatment after neoadjuvant chemotherapy. There are no guidelines of the management for these patients. Before designing clinical trials, we conducted this study to investigate their characteristics, reasons of dropout, and the follow-up information. METHODS: Medical records were consecutively reviewed of patients with locally advanced oral cavity cancer who underwent neoadjuvant chemotherapy from Jan 2017 to Dec 2019.Variables were compared between patients stopped treating after chemotherapy and completed treatments by student t-test and Chi-square test. Logistic regression model was used to calculate the odd rations of potential predictors of dropout. The dropout patients were followed up for reasons and results of their decision. RESULTS: A total of 171 patients were included with 23 not undergoing surgery after chemotherapy. The odd ratios of age over 65 and single marital status were 3.11 (95%CI: 1.1, 8.7) and 4.935 (95%CI: 1.5, 16.1), respectively, for the dropout. The median survival of patients without surgery was 7.4 months. Believing that chemotherapy would be effective and being afraid of the consequence of surgery were the main reasons of refusing surgery. CONCLUSIONS: The prognosis was poor of these dropout patients. Symptom relief and fear of surgery were the reasons of dropout. Age and marital status affected their decision. Clinical trials are needed to be designed for these patients.

Assessing the magnetic resonance imaging in determining the depth of invasion of tongue cancer.

OBJECTIVES: To assess the magnetic resonance imaging (MRI) in predicting tumour's depth of invasion (DOI) of tongue cancer by comparing to pathology and to determine the cut-off value of MRI-derived DOI for lymph node metastasis. PATIENTS AND METHODS: In a retrospective analysis, 156 patients with newly diagnosed tongue cancer were included. Tumour's DOI was compared between MRI measurement and pathology by Pearson correlation coefficient and paired t test. The accuracy of MRI-derived DOI was compared to the pathological DOI. The relationship between MRI-derived DOI and cervical lymph node metastasis was calculated by receiver operating characteristic curve. RESULTS: Tumour's DOI was well correlated between MRI measurement and pathology with correlation coefficients of 0.77. MRI-derived DOI was 3.4 mm (28%) larger than pathology. The accuracy of MRI in deciding pathological DOI was 67.9%. The cut-off value of MRI-derived DOI was 10.5 mm for lymph node metastasis of tongue cancer. CONCLUSION: Magnetic resonance imaging can be used as a reference to determine tumour's DOI of tongue cancer. Tumour with MRI-derived DOI larger than 10.5 mm deserves simultaneous neck dissection at initial surgery.

Salivary gland carcinoma in Shanghai (2003-2012): an epidemiological study of incidence, site and pathology.

BACKGROUND: Salivary gland carcinoma ranks the sixth in head and neck cancers while it is relatively rare in its incidence. Epidemiological studies have been based mostly on institutional data, leading to selection bias in incidence evaluation. Most population-based cancer registries have grouped cancers of the minor salivary glands with oral cancer instead of with salivary gland carcinoma as a whole, because of the international disease coding. Thus, the incidence of salivary gland carcinoma has not been well assessed. The aim of the study is to evaluate the incidence of both minor and major salivary gland cancers in Shanghai during the years 2003-2012, and to analyse the site and histological distributions. METHODS: Data from the Shanghai Cancer Registry system were extracted for patients diagnosed with malignancies of the major or minor salivary glands for the year 2003 to 2012. Pertinent socio-demographic data were obtained from the Shanghai Municipal Bureau of Public Security. The age-standardized incidence rates were calculated directly according to the world standard population. The change in incidence during the study period was analysed by comparing the rates during the first and next five years. The distributions of anatomic subsites and histology were also analysed. RESULTS: A total of 1831 cases were identified, representing 0.35% of all malignancies during the study period. The median age was 59 and 57 years for men and women, respectively. The age-standardized incidence was 7.99 per 1,000,000 person-year, with a male-to-female ratio of 1.10. There was no significant change in the incidence during the 10-year period. The anatomic distribution confirmed the 4:1:2 rule for the parotid, submandibular, and minor glands. In men, adenocarcinoma not otherwise specified was the most common histological type followed by mucoepidermoid; in women, the mucoepidermoid was the most common histotype, followed by the adenoid cystic. CONCLUSION: Salivary gland carcinoma is relatively rare in incidence. However, the variations in age and sex distribution in sites and histology types suggest differences in aetiology which warrants further investigation.

Oral cancer incidence in Shanghai ---- a temporal trend analysis from 2003 to 2012.

BACKGROUND: Oral cancer is a serious problem owing to its poor prognosis and destruction of patients' eating ability as well as facial appearance. Epidemiological studies can provide aetiological clues for prevention. The prevalence of oral cancer in densely populated cities in eastern China is unclear. The aim of the study is to analyse the incidence rates of oral cancer in Shanghai over the period 2003-2012 and estimate the temporal trends. METHODS: Cases of oral cancer were retrieved from the Shanghai Cancer Registry system in the Shanghai Municipal Center for Disease Control & Prevention for the years 2003 to 2012. Information on the corresponding population was obtained from the Shanghai Municipal Bureau of Public Security. Age-standardised incidence rates were directly calculated according to the world standard population. An annual percent change model was employed to analyse the temporal trends of cancer incidence. RESULTS: A total of 3860 oral cancer cases were reported, representing 0.69% of all malignancies in Shanghai during the 10-year study period. The mean age at diagnosis was 64 years. The age-standardised incidence rate was 1.34 per 100,000 person-years, with a male-to-female ratio of 1.41. Annually, the incidence rates increased by 3.83 and 2.54% for men and women, respectively. The increase was most noticeable in males aged 45-64 years. CONCLUSION: In Shanghai, the oral cancer incidence is relatively low. However, it is continuously increasing, especially among middle-aged males. This finding urges further investigations on the risk factors of oral cancer in this population, especially on changes in living patterns, such as the smoking, drinking, and dietary habits.

Estimate of Health Burden on Smoking-associated Oral Cancer in Shanghai and its Surrounding Areas.

OBJECTIVE: To evaluate the temporal trend of inpatients with smoking-associated oral cancer in Shanghai and its surrounding areas and to forecast the public health burden in the next decade. METHODS: Data of inpatients with oral cancer were retrieved from Shanghai Ninth People's Hospital during a 15-year period. The annual numbers of inpatients were compared by Chi-test. The hospitalization expenditures were compared by Student's t test. The trend analysis and inpatient forecasting were performed by exponential smoothing, regression models, and the forecasting function in Excel software. The financial burden of smoking-associated oral cancer was calculated by polynomial equation. RESULTS: The annual number of inpatients with oral cancer increased during the study period. Most male patients were reported to have a smoking habit. Among the three estimation methods, polynomial regression model was most fitted to the existing data. By a conservative estimation, the public health burden of smoking-associated oral cancer patients will be 120 million RMB by the year 2026, not including the cost by prevalent patients and the patients' family members. CONCLUSION: Smoking-associated oral cancer will cost a lot of public resource in the next decade. Efforts should be made to lower the amount of tobacco consumption.

Tea consumption and the risk of oral cancer incidence: a case-control study from China.

OBJECTIVES: To evaluate the relation of tea consumption with the risk of oral cancer incidence. SUBJECTS AND METHODS: A multicenter case-control study based on hospitalized population was conducted for evaluating the association of tea consumption with oral cancer risk in China. Black tea and green tea were separately analyzed. 723 cases and 857 controls were included. Unconditional multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of oral cancer for tea consumption. RESULTS: The ORs for green tea consumption⩾8g/day compared with<4g/day were 0.72 (95% CI 0.54, 0.93) for men, and 0.93 (95% CI 0.74, 1.26) for women. The ORs for black tea consumption⩾6g/day compared with<2g/day were 0.97 (95% CI 0.74, 1.20) for men, and 0.91 (95% CI 0.68, 1.23) for women. Green tea intake was significantly associated with reduced risk of oral cancer in men, but not in women, and the association was stronger in heavily smoking men. There was no indication that black tea consumption was associated with decreased oral cancer risk. CONCLUSION: The results of this study indicated that green tea consumption may decrease the risk of oral cancer in men especially for those smoking heavily.

[Lipoma in the floor of mouth: a case report and literature review].

It's uncommon for lipoma growing beneath the mucosa of the floor of mouth. A case of lipoma in the floor of mouth was reported. The clinical feature and key points of treatment were discussed based on literature review.

Norcantharidin inhibits growth of human gallbladder carcinoma xenografted tumors in nude mice by inducing apoptosis and blocking the cell cycle in vivo.

BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Bax, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm3, P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 and Bax proteins/mRNAs in the NCTD group compared with the control group. CONCLUSION: NCTD inhibits the growth of xenografted tumors of human gallbladder carcinoma in nude mice by inducing apoptosis and blocking the cell cycle in vivo.

[Ectopic meningioma in oral and maxillofacial region: report of 23 cases].

PURPOSE: To analyse the clinical features and treatment of ectopic meningioma (EM) in oral and maxillofacial region. METHODS: Twenty-three cases of EM in the oral and maxillofacial region from 1990 to 2008 were reviewed. The clinical features, image findings, surgical treatment and follow-up results were analyzed. RESULTS: The median age of these patients was 37 years old and there was no gender predilection, but there were more female patients in the group of over 40 years old. The primary sites of the tumor were parapharyngeal space(13), infratemporal space/ pterygopalatine space(5), temporal region(3),orbital area (1) and buccal mucosa(1). The CT image of EM in the oral and maxillofacial region was similar to that in the brain. All 23 cases underwent surgical treatment, seventeen cases underwent the tumor totally resected and 6 cases underwent partially resected. Twelve cases were followed up, in which 3 cases recurred and 8 cases had a long-term nerve injury. CONCLUSIONS: EM in the oral and maxillofacial region mainly occurs in adolescent, middle-aged patients and females over 40 years old. The predilection site of the tumor is the deep space of oral and maxillofacial region with adherence to the cervical sheath and lower cranial nerves. Preoperative CT scan is helpful for diagnosis. The main choice of treatment is total resection. The main complication is nerve injury.

[Application of individualized free anterolateral thigh combined flap for tongue and mouth floor defects resulted from tongue carcinoma].

OBJECTIVE: To investigate the application of individualized free anterolateral thigh combined flap (ALTCF) for tongue and mouth floor defect resulted from tongue carcinoma. METHODS: From 2006 to 2008, individualized ALTCFs were used in 31 cases of tongue and mouth floor defects resulted from tongue carcinoma. The nutritional perforator vessel was musculocutaneous pattern in 22 cases and septocutaneous pattern in 9 cases. The size of the flaps and the included muscle was (4-8) cm x (5-10) cm and (2-5) cm x (3-6) cm, respectively. The length of blood vessel pedicle was (6.81 +/- 3.23) cm. RESULTS: All the 31 free flaps survived with primary healing and no complication. The appearance and function were both satisfactory. During the follow-up period of 1-3 years, 28 cases survived, 2 cases were reoperated due to the neck lymphatic metastasis on the contralateral side. 1 case died of distant metastasis. CONCLUSIONS: Individualized ALTCF is a reliable flap for the tongue and month floor defects resulted from tongue carcinoma. Both the cosmetic and functional results are satisfactory with less morbidity in donor site and less complication.

[Self-healing Langerhans cell histiocytosis in a child: case report and literature review].

Langerhans cell histiocytosis is an entity of Langerhans cell with its proto-cell proliferating locally or disseminatively. Children below 3 years old always present an acute disseminated type. The responsible cell involves in multiple systems and the viscera, so it often undergoes a poor prognosis. Without medical interference, the natural course of the disease may be within 6 months. But in this paper, a 19-month-old child was reported who was diagnosed Langerhans cell histiocytosis by biopsy and self-healed without treatment. After over 9 years of follow-up, no recurrence was found.

[Clinical and pathological analysis of central compartment dissection in patients with papillary thyroid cancer with negative clinical lymph node metastasis].

OBJECTIVE: To assess the significance of central compartment dissection in papillary thyroid cancer with negative clinical lymph node metastasis. METHODS: Clinical and pathological data of 641 papillary thyroid cancer patients with negative clinical lymph node metastasis who were treated from January 1998 to April 2006 were collected. The positive rate of the lymph nodes metastasis was analyzed. The relations between the central compartment lymph nodes and the patients' gender, age, tumor size and number were concerned. Among the 641 cases, 114 case who received operation more than five years were followed up for the relations between the pathological status of central compartment lymph nodes and ipsilateral neck metastasis or contra thyroid lobe recurrence. RESULTS: The median number of the central compartment lymph nodes was 4 each case and 53.0% (340/641) cases of papillary thyroid cancer patients with negative clinical lymph node metastasis had positive central compartment lymph nodes metastasis. Large tumor size and multiple origins were related to central compartment lymph nodes involvement, but the patients' gender or age was not. In the 114 follow-up cases, ipsilateral neck metastasis occurred in 12 cases, among which 11 cases had high positive central compartment lymph nodes metastasis. Contra thyroid lobe recurrence occurred in 5 cases, whose statuses of central compartment lymph nodes were different. CONCLUSIONS: Papillary thyroid cancer patients with negative clinical lymph node metastasis deserve formal central compartment dissection. The pathological status of central compartment lymph nodes relates to the tumor size and number. High positive rate of central compartment lymph nodes may lead to possible ipsilateral neck metastasis.

Inhibitory effect of norcantharidin on the growth of human gallbladder carcinoma GBC-SD cells in vitro.

BACKGROUND: Gallbladder carcinoma is a lethal malignant neoplasm with dismal surgical results. Unfortunately, the adjuvant therapies for gallbladder carcinoma such as chemotherapy and radiotherapy are also disappointing. We reported that norcantharidin (NCTD), a demethylated form of cantharidin, which is an active ingredient of the Chinese medicine Mylabris, was used against human gallbladder carcinoma GBC-SD cells. In the present study, we further studied the mechanism underlying the inhibitory effect of NCTD on growth of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: Human gallbladder carcinoma GBC-SD cells were grown in cell culture and divided into a NCTD group and a control group. The inhibitory effect of NCTD on growth of GBC-SD cells was investigated by evaluation of proliferation, cell cycle, apoptosis and morphological changes of the cells. Cell proliferation was assessed by tetrazolium-based colorimetric assay. The induction of cell cycle arrest and apoptosis was measured by flow cytometry. The morphological changes of the cells were observed by light- and electron-microscopy. To elucidate the anticancer mechanism of NCTD, expression of the proliferation-related gene proteins PCNA, Ki-67, cyclin-D1 and p27 and the apoptosis-related gene proteins Bcl-2, Bax and Survivin were determined by the streptavidin-biotin complex method and RT-PCR. RESULTS: NCTD inhibited the proliferation of GBC-SD cells in a dose- and time-dependent manner, with an IC50 of 56.18 microg/ml at 48 hours. The flow cytometric profiles revealed that NCTD (at the IC50 for 48 hours) significantly increased the proportion of cells in G2/M phase and significantly decreased the proportion of cells in S phase, with a significantly increased rate of cell apoptosis. After treatment with the 48-hour IC50 dose of NCTD, cell shrinkage, vacuolar cytoplasm, membrane budding, karyorrhexis, karyolysis, chromosome condensation and chromatin aggregation in some GBC-SD cells were observed by light-microscopy; decreased microvilli, Golgiosome atrophy, mitochondrial swelling, nuclear shrinkage, chromosome condensation and typical apoptosis bodies were seen by electron-microscopy, and the morphological changes of apoptosis occurred in GBC-SD cells. The expression of PCNA, Ki-67 and Bcl-2 proteins decreased significantly; the Pix or relative levels of PCNA mRNA, cyclin-D1 mRNA, Bcl-2 mRNA and Survivin mRNA decreased significantly, whereas the Pix or relative levels of p27 mRNA and Bax mRNA increased significantly. CONCLUSIONS: NCTD inhibits the growth of human gallbladder carcinoma GBC-SD cells in vitro. Its anticancer mechanism may correlate with inhibition of cell proliferation, arrest of the cell cycle, blockage of DNA synthesis, influence on cell metabolism, induction of cell apoptosis and influence on expression of the proliferation-related genes PCNA, Ki-67, cyclin-D1 and p27, and the apoptosis-related genes Bcl-2, Bax and Survivin in human gallbladder carcinoma GBC-SD cells.

[Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo].

OBJECTIVE: To explore the anti-tumor mechanism of norcantharidin (NCTD) for the implanted tumors of human gallbladder carcinoma in nude mice in vivo. METHODS: Animal model of implanted tumors of human gallbladder carcinoma in nude mice was established. Mice were randomly divided into control, 5-FU, NCTD and NCTD + 5-FU groups and were taken different treatment. The expressions of PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23/nm23-H1, MMP2 and TIMP2 proteins or genes in each tissue section of every group were determined by immunohistochemistry and RT-PCR. RESULTS: (1) On proliferation-related gene proteins, the expression of PCNA, Ki-67, cyclin D1 was significantly decreased, with significantly increased expression of p27 protein, in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of PCNA mRNA, cyclin D1 mRNA was decreased, with significantly increased expression of p27 mRNA in NCTD group. (2) On apoptosis-related gene proteins, the expression of Bcl-2 was significantly decreased in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of Bcl-2 mRNA, Survivin mRNA was significantly decreased, with significantly increased expression of Bax mRNA in NCTD group. (3) There was significant difference on invasion around tumor and lung metastasis in NCTD group when compared with control group (P < 0.01). On metastasis-related gene proteins, the expression of nm23 and TIMP2 was significantly increased, with significantly decreased expression of MMP2 in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of nm23-H1 mRNA, TIMP2 mRNA was significantly increased, with significantly decreased expression of MMP2 mRNA in NCTD group. CONCLUSIONS: The anti-tumor mechanism of NCTD for human gallbladder carcinoma in nude mice might correlated with inhibition of cell proliferation, blockage of cell cycle, induction of cell apoptosis, reducing of cell motility and invasive capability, alteration of the expression of proliferation-, apoptosis- and metastasis-related gene proteins such as PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23, MMP2 and TIMP2.

Effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells.

AIM: To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. METHODS: Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique. The growth and the invasiveness of GBC-SD cells in vitro were evaluated by the tetrazolium-based colorimetric assay and by the Matrigel experiment and the crossing-river test. Expression of PCNA, Ki-67, MMP2 and TIMP2 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. RESULTS: In vitro norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose- and time-dependent manner, with the IC50 value of 56.18 microg/mL at 48 h. Norcantharidin began to inhibit the invasion of GBC-SD cells at the concentration of 5 microg/mL, and the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly at 40 microg/mL. After treatment with norcantharidin, the expression of PCNA, Ki-67, and MMP2 was significantly decreased. With the increase in TIMP2 expression, the MMP2 to TIMP2 ratio was decreased significantly (P<0.05). CONCLUSION: Norcantharidin inhibits the proliferation and growth of human gallbladder carcinoma cells in vitro at relatively low concentrations by inhibiting PCNA and Ki-67 expression. Its anti-invasive activity may be the result of decrease in MMP2 to TIMP2 ratio and reduced cell motility.

Influence of norcantharidin on proliferation, proliferation-related gene proteins proliferating cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC-SD cells.

BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be considered for palliative treatment such as chemotherapy and radiotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carcinoma were cultured by the cell culture technique. The experiment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose-and time-dependent manner, with the IC50 value of 56.18 microg/ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932+/-0.031 vs. 0.318+/-0.023, P<0.001) and Ki-67 (0.964+/-0.092 vs. 0.297+/-0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expression of their proliferation-related gene proteins PCNA and Ki-67.

[The in vitro effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells and its mechanism].

OBJECTIVE: To study the effect and mechanism of action of norcantharidin on proliferation and invasion of GBC-SD cells. METHODS: GBC-SD cells of human gallbladder carcinoma were cultured by cell culture technique. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The Matrigel experiment and the crossing-river test were used to examine the invasiveness of GBC-SD cells. Expression of MMP(2), TIMP(2), PCNA and Ki-67 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. RESULTS: Norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose and time dependent manner, with an IC(50) value of 56.18 micro g/ml at 48 h. The Matrigel experiment showed that norcantharidin began to inhibit the in vitro invasion of GBC-SD cells at the concentration of 5 micro g/ml. At 40 micro g/ml, the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly. After treatment with norcantharidin, the expression of PCNA, Ki-67, MMP(2) was significantly decreased. With the increase in TIMP(2) expression, the MMP(2) to TIMP(2) ratio was decreased significantly (P < 0.05). CONCLUSION: Norcantharidin inhibits the in vitro proliferation and growth of human gallbladder carcinoma cells at relatively low concentrations by inhibiting PCNA and Ki-67 expression. Its anti-invasive activity may be the results of decrease in MMP(2) to TIMP(2) ratio and reduced cell motility.