A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model.
BACKGROUND
We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF-kappaB) activation, and that blockade of NF-kappaB activation augments TXT-induced apoptosis in human gastric cancer cells. In addition, we have also shown that a protein-bound polysaccharide PSK enhances TXT-induced apoptosis through NF-kappaB inhibition in human pancreatic cancer cells. Based on these observations, in the present study the possibility that PSK could enhance TXT-mediated tumor suppression was examined in vivo and in vitro.


METHODS
A gastric cancer xenograft model was used to examine the enhanced TXT-mediated tumor suppression by PSK in vivo. The effects of PSK on proliferation and apoptosis induced by TXT in gastric cancer cells were evaluated in vitro using a human gastric cancer cell line, MK-1. The effect of PSK on increased TXT-induced invasion was also measured.


RESULTS
PSK enhanced TXT-mediated tumor suppression in vivo. Immunohistochemical analyses of the tumors revealed that TXT increased NF-kappaB activation in the tumors and this was suppressed by PSK. In the ex vivo experimental system, PSK enhanced the growth inhibition and apoptosis induced by TXT in the MK-1 cells and reduced the increased invasive ability induced by TXT.


CONCLUSIONS
PSK enhanced TXT-induced tumor suppression in a gastric cancer xenograft model.
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Akio
A
Yamasaki
Momoko
M
Shoda
Hiroko
H
Iijima
Shuntaro
S
Nagai
Junji
J
Wada
Hiroyuki
H
Suzuki
Nobuhito
N
Chikazawa
Takehiko
T
Tasaka
Chizu
C
Kameda
Haruo
H
Tanaka
Mio
M
Ikebe
Ei
E
Jo
Norihiro
N
Sato
Masafumi
M
Nakamura
Fujio
F
Sekine
Takashi
T
Morisaki
Mitsuo
M
Katano
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011509:Proteoglycans / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D016328:NF-kappa B; D011509:Proteoglycans; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; C010770:polysaccharide-K