Multidrug Resistance Phenotype and Paclitaxel (Taxol®) Sensitivity in Human Renal Carcinoma Cell Lines of Different Histologic Types

The network of P-glycoprotein and microRNAs interactions

“…[21][22][23][24]26 Renal Cancer P-gp transcripts or protein identified in normal renal proximal tubules and in the majority of renal cell carcinoma samples indicated that this efflux pump is implicated in both intrinsic and acquired resistance. [27][28][29][30][31][32][33] Liver Cancer Overexpression of P-gp (but not MRP1) mainly contributes to the MDR of SMMC-7721/ADM cells. The upregulation of P-gp and BCRP (but not of MRP1 and LRP) were involved in the MDR of HepG2/ADM cells.…”

Resistance to Microtubule-Stabilizing Drugs Involves Two Eventse: β-Tubulin Mutation in One Allele Followed by Loss of the Second Allele

“…Several mechanisms of resistance to Taxol have been described. With the exception of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR) 2,3 , all these mechanisms involve alterations in tubulin. Such alterations include: (1) altered expression of β-tubulin isotypes in Taxol-resistant cells and Taxol-resistant ovarian tumors; [4][5][6] (2) increased microtubule dynamics in Taxol-resistant cancer cells, 7 and importantly, (3) the presence of β-tubulin mutations in Taxol-resistant cells.…”

“…With the exception of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR) 2,3 , all these mechanisms involve alterations in tubulin. Such alterations include: (1) altered expression of β-tubulin isotypes in Taxol-resistant cells and Taxol-resistant ovarian tumors; [4][5][6] (2) increased microtubule dynamics in Taxol-resistant cancer cells, 7 and importantly, (3) the presence of β-tubulin mutations in Taxol-resistant cells. 8,9 The epothilones are novel microtubule-stabilizing natural products of soil bacteria origin, that compete with Taxol for the same binding site on β-tubulin but maintain activity against Pgp-expressing MDR cells.…”

Intrinsic chemotherapy resistance to the tubulin‐binding antimitotic agents in renal cell carcinoma

“…PgP has been implicated in both intrinsic and acquired resistance in a number of cancers, including RCC, where PgP transcripts or protein have been identified in normal renal proximal tubules 4 and in the majority of RCC samples, [5][6][7][8][9] often at higher levels than other tumor types. Experimental data also supporting a role for PgP in RCC resistance include high PgP mRNA levels in several renal tumor cell lines examined as part of the National Cancer Institute (NCI) in vitro anticancer drug screen (http://dtp.nci.nih.gov), 10,11 and increased PgP mRNA levels associated with in vitro resistance of cell lines or primary cultures to paclitaxel 12 and doxorubicin. 13 Evidence that chemoresistance in RCC is not exclusively determined by PgP is provided by the observations that some primary cell lines or cultures are resistant in the absence of detectable PgP expression and the resistance is not reversed by inhibitors of PgP.…”

“…13 Evidence that chemoresistance in RCC is not exclusively determined by PgP is provided by the observations that some primary cell lines or cultures are resistant in the absence of detectable PgP expression and the resistance is not reversed by inhibitors of PgP. 6,12,14,15 Clinical studies to date have failed to provide convincing evidence for PgP-mediated resistance in RCC, with trials of PgP antagonists having limited success, 2 although this may be attributed to lack of potency and specificity of the early-generation antagonists. 16 Other members of the ABC transporter family such as the multidrug resistance-associated proteins (MRPs) have also been implicated in drug resistance.…”