PMID- 19080633
OWN - NLM
STAT- MEDLINE
DCOM- 20090528
LR  - 20181201
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 88
IP  - 35
DP  - 2008 Sep 16
TI  - [Tumor growth inhibition of paclitaxel-octreotide conjugates on human non small 
      cell lung cancer: experiment with mice].
PG  - 2498-503
AB  - OBJECTIVE: To evaluate the antitumor effects of the conjugates synthesized by 
      coupling cytotoxic paclitaxel (PTX) to somatostatin analog octreotide (OCT) on 
      human non small cell lung cancer (NSCLC). METHODS: Two cytotoxic somatostatin 
      analog, PTX-OCT and 2PTX-OCT, were developed in which PTX was linked to 
      octreotide. Forty-five BALB/c nu/nu nude mice were injected with human NSCLC 
      cells of the line A549 into the right armpit. The nude mice that were xenografted 
      were randomly divided into 8 groups. (1) control group (n = 6), (2) PTX-OCT group 
      (n = 5), injected intravenously with PTC-OCT 150 nmol/kg on days 1, 7, and 21, 
      (3) 2PTX-OCT group (n = 6), injected intravenously with PTC-OCT 150 nmol/kg, (4) 
      OP group (n = 6), injected with mixture of PTX and OCT 150 nmol/kg, (5) OCT group 
      (n = 5) injected with OCT 150 nmol/kg (6) PTX group (n = 6), injected with PTX 
      150 nmol/kg, (7) 2PTX group, injected with PTX 300 nmol/kg, and (8) 2(PTX-OCT) 
      injected with PTX-OCT 300 nmol/kg, The tumor volume and body weight (BW) were 
      observed regularly. The tumor volume doubling time was calculated. White blood 
      cells were counted by collecting peripheral blood sample. By the end of 
      experiment the mice were killed with the tumors taken out. The expression of mRNA 
      of subtypes1-5 of human somatostatin receptor (SSTR1-SSTR5) were investigated 
      using RT-PCR. Histological apoptosis was detected by DNA ladder. 
      Immunohistochemistry was used to examine the SSTR2 and SSTR5 expression and tumor 
      microvessel density (MVD). RESULTS: The tumor volumes of 2PTX-OCT and 2(2PTX-OCT) 
      groups were significantly smaller than those of other groups (all P < 0.01). The 
      tumor doubling times of the 2PTX-OCT and 2 (2PTX-OCT) groups were significantly 
      longer than those of the other groups too (all P < 0.01). The MVD levels of the 
      2PTX-OCT and 2 (2PTX-OCT) groups were significant lower than those of the other 
      groups (all P < 0.01). The toxicity of the PTX group was more obvious. The WBC 
      count levels of the PTX and 2PTX groups were significantly lower than those of 
      the other groups (all P < 0.05). mRNA expression could be found for SSTR1, 2, 4, 
      and 5 in the A549 xenografts. Immunohistochemistry showed that SSTR2 was mainly 
      found in the tumor cell membrane, and SSTR5 was found in the tumor cell membrane 
      and cytoplasm. More histological apoptosis bands were shown by DNA ladder method 
      in the 2PTX-OCT and 2 (PTX-OCT) groups. CONCLUSION: The targeting conjugate 
      2PTX-OCT inhibits the proliferation of tumor cells, reduces microvessel, and 
      decreases the toxicity in comparison with the cytotoxic radical PTX.
FAU - Shen, Hong-Chang
AU  - Shen HC
AD  - Department of Oncology, Qilu Hospital, Shandong University, Jinan 250012, China.
FAU - Wang, Xiu-Wen
AU  - Wang XW
FAU - Liu, Yan-Guo
AU  - Liu YG
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Somatostatin)
RN  - 0 (Sstr2 protein, mouse)
RN  - 8X85ZJG6XJ (somatostatin receptor 5)
RN  - P88XT4IS4D (Paclitaxel)
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/blood supply/*drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Humans
MH  - Lung Neoplasms/blood supply/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microvessels
MH  - Octreotide/*therapeutic use
MH  - Paclitaxel/*therapeutic use
MH  - RNA, Messenger/genetics
MH  - Receptors, Somatostatin/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2008/12/17 09:00
MHDA- 2009/05/29 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/05/29 09:00 [medline]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2008 Sep 16;88(35):2498-503.