Search

Non-small-cell lung carcinoma is generally refractory to chemotherapy. The difficulties that arise in the treatment of this type of tumor make it necessary to develop new therapeutic strategies. Previous work done in our laboratory showed that a marine substance named bistramide K induced in vitro (atypical) terminal differentiation of NSCLC-N6 cell line. This activity is linked to a growth arrest of NSCLC-N6 cell line and an irreversible block at the G1 phase of the cell cycle (G1DT). In order to identify the genes that could be expressed after the treatment by the drug, we constructed a subtractive cDNA library with enriched mRNA extracted from BK-treated NSCLC-N6. After differential hybridization and DNA sequencing, we identified two sequences. The sequence identified for the clone 8 showed strong homology to the sequence of the ribosomal protein L35A. The sequence identified for the clone 4 did not show any homology with known sequences in official gene data banks.

Non-small-cell lung carcinoma (NSCLC) is a particularly serious disease because of its chemoresistance to current treatments. To investigate the nature of his generally innate resistance, we cloned an established cell line (NSCLC-N6) derived from a non-small cell bronchopulmonary carcinoma. Four cell subpopulations (C15, C65, C92 and C98) were isolated from the mother line. These four clones were studied in comparison with each other for cell doubling time in vitro, ploidy, chemosensitivity in vitro, cytogenetic, expression of the oncogene erb-B2 and other tumor markers (Kr, CEA and Chr A). Each clone shows a distinct biologic pattern for various biological parameters. Our results indicated hat cell doubling time (in vitro) increased when the hyperploid population was prevailing. The clones differ in their chemosensitivity to therapeutic agents. This cellular diversity might help to explain why these tumors are chemoresistant. This heterogeneity within NSCLC tumors should be taken into consideration in the choice of treatment.

The correlation between the degree of expression of the multidrug resistance-1 (MDR-1) gene and the process of differentiation into non-small-cell, bronchopulmonary carcinoma was studied in vitro and in vivo. For this purpose, a technique for the quantitative analysis of MDR-1 gene expression was developed by competitive reverse-transcriptase polymerase chain reaction. The study of 9 epidermoid carcinomas with various degrees of differentiation did not enable us to establish a correlation in vivo in the patient. However, an in vitro study performed on a non-small-cell lung carcinoma cell line and two of its clones showed that MDR-1 gene expression increased with the degree of differentiation, which was confirmed in vivo when this line was xenografted into nude mice.

Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown to be endowed with inhibitory effects cell growth in various experimental models. We studied both the antiproliferative and antitumor properties of a fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a cell line derived from a non-small-cell human bronchopulmonary carcinoma (NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in vitro a reversible antiproliferative activity with a block observed in the G1 phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show antitumor activity at subtoxic doses. These preliminary results indicate that HF exhibits inhibitory effect both in vitro and in vivo and is very potent antitumor agent in cancer therapy.