Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

“…However, resistant subline exerted increased Bcl-2, survivin and c-IAP-1 levels accompanied by a marked decrease of p53 in all treatments. This corresponded to several findings, when Bcl-2 and Bcl-xl [27,28,29] protein over-expression is often, but not always [29], associated with CDDP resistance, and when Bcl-2 or Bcl-xl antagonists augmented CDDP efficacy [31,32]. In parental human bladder cancer cells, in response to CDDP, up-regulation of Bax was time-dependent and resulted in apoptosis.…”

TCEAL7, a putative tumor suppressor gene, negatively regulates NF-κB pathway

“…Other reports have shown an association of ICAM expression with resistance in ovarian carcinoma (Giavazzi et al, 1994;Opala et al, 2003). Bcl-xl, an antiapoptotic gene, has been shown to be overexpressed in ovarian tumors and is correlated with shorter diseasefree survival after chemotherapy and recurrent disease (Williams et al, 2005;Kar et al, 2007). We have previously reported that TCEAL7 expression is lost in early-stage ovarian tumors (Chien et al, 2005).…”

The p53 Upregulated Modulator of Apoptosis (PUMA) Chemosensitizes Intrinsically Resistant Ovarian Cancer Cells to Cisplatin by Lowering the Threshold Set by Bcl-xL and Mcl-1

“…Previous studies have shown that expression of Bcl-x L in ovarian carcinoma is associated with chemoresistance and recurrent disease and that Bcl-x L downregulation in response to cisplatin is absent in chemoresistant ovarian carcinoma cells (32,34). Moreover, in ovarian carcinoma, Bcl-2 and Bcl-x L proteins are frequently overexpressed (34,(47)(48)(49) and appear to be involved in chemoresistance (34,47,(49)(50)(51).…”

“…Previous studies have shown that Bcl-2 and Bcl-x L proteins are frequently overexpressed (34,(47)(48)(49) and appear to be involved in chemoresistance in ovarian carcinoma (34,47,(49)(50)(51). Furthermore, chemoresistance of ovarian carcinoma has been shown to associate with the absence of Bcl-x L expression downregulation in response to cisplatin (32,34). More recently, it was reported that Bcl-x L and Mcl-1 are able to cooperate to protect ovarian carcinoma cells against oncogenic stress or chemotherapy-induced apoptosis (52).…”

“…In this work, to investigate whether PUMA could induce apoptosis of intrinsically resistant ovarian cancer cells, we selected the cisplatin-resistant SKOV3 (p53 double deletion mutant, p53 -/-) human ovarian carcinoma cell line as a model of intrinsic resistance (31)(32)(33) and the cisplatin-sensitive A2780s (p53 wild-type, p53 WT) human ovarian carcinoma cell line, which was derived from an untreated patient with primary ovarian carcinoma (33,34), as a model of intrinsic chemosensitivity, respectively. We examined the regulation of PUMA by cisplatin in both A2780s (p53 WT) and SKOV3 (p53 -/-) ovarian carcinoma cell lines and evaluated the effect of PUMA on the chemotherapeutic efficacy of cisplatin in A2780s and SKOV3 ovarian cancer models in vitro and in vivo.…”